the following table provides a dictionary of the terms used in the description of the instant invention . table i______________________________________abbreviateddesignation______________________________________ amino acidgly glycinephe l - phenylalaninecad 2 ( . sub .-- s )- amino - 3 ( . sub .-- r ), 4 ( . sub .-- s )- dihydroxy - 1 - cyclohexyl - 6 - methylheptanecah 1 ( . sub .-- s )- amino - 2 ( . sub .-- r ), 3 ( . sub .-- s )- dihydroxy - 1 - cyclohexyl - 5 - methylhexaneasta 3 ( . sub .-- r , . sub .-- s ), 4 ( . sub .-- s )- diamino - 6 - methylheptanoic acidacys 3 ( . sub .-- r , . sub .-- s ), 4 ( . sub .-- s )- diamino - 5 - cyclo - hexanepentanoic aciddfsta 4 ( . sub .-- s )- amino - 3 ( . sub .-- s )- hydroxy - 2 , 2 - difluoro - 6 - methyl - heptanoic aciddfksta 4 ( . sub .-- s )- amino - 3 - oxo - 2 , 2 - difluoro - 6 - methylheptanoic aciddfcys 4 ( . sub .-- s )- amino - 3 ( . sub .-- s )- hydroxy - 2 , 2 - difluoro - 5 - cyclohexane - pentanoic aciddfkcys 4 ( . sub .-- s )- amino - 3 - oxo - 2 , 2 - difluoro - 5 - cyclohexane - pentanoic acid acyl groupz benzyloxycarbonylboc tert - butyloxycarbonyliva isovalerylnva n - valerylsmo morpholinosulfamylsme dimethylaminosulfamyl amides withaem 4 -( 2 - aminoethyl ) morpholinemba 2 ( . sub .-- s )- methylbutylamine ## str4 ## 2 - aminomethylpyridinenhch . sub . 2 ph benzylaminenhc . sub . 4 h . sub . 9 n - butylaminenhch . sub . 3 methylamine ## str5 ## m - xylene - di - amine solvents and reagentshobt hydroxybenzotriazole hydratedmf n , n - dimethylformamideet . sub . 3 n triethylaminedcc n , n &# 39 ;- dicyclohexyl - carbodiimidethf tetrahydrofuranmeoh methanolet . sub . 2 o diethyl ethercdi carbonyldiimidazoleetoh ethanoltbdms tert - butyldimethylsilanetfa trifluoroacetic acidhoac acetic acidetoac ethyl acetate______________________________________ compounds of the instant invention are represented by formula ## str6 ## or a pharmaceutically acceptable acid addition salt thereof wherein : a is hydrogen , boc , z , lva , nva , or ## str7 ## wherein r 2 and r 3 are each independently hydrogen , a straight or branched lower alkyl , or r 2 and r 3 when taken together with the nitrogen to which they are attached form a saturated 5 - or 6 - membered ring which may optionally contain an additional heteroatom : o , s , or nr 3 , r 1 is ch 2 ph , ## str8 ## [ isosterel ] is [ chohch 2 ], [ coch 2 ], [ chohchoh ], [ ch ═ ch ], ## str9 ## [ ch 2 nh ], [ ch 2 noh ], [ ch 2 s ], [ ch ( nh 2 ) ch 2 ], [ ch 2 so ], ch 2 so 2 ], [ ch 2 ch 2 ], , [ chohchohchohco ] or [ ch 2 o ] wherein r ∝ is h , lower alkyl , lower alkenyl , lower alkynyl , co 2 r 3 , arylmethyl , or heterocyclicmethyl ; r 5 is hydrogen , or 6 , s ( o ) n r 6 , nr 7 r 8 or nhcor 9 wherein r 6 is lower alkyl , lower alkenyl , lower alkynyl , aryl , or heteroaryl , n is an integer of from 0 to 2 , r 7 and r 8 are each independently hydrogen , lower alkyl , lower alkenyl , lower alkynyl , aryl or heteroaryl or when taken together with the nitrogen to which they are attached form a saturated 5 - or 6 - membered ring which may optionally contain an additional heteroatom , o , s , or nr 3 , r 9 is hydrogen , lower alkyl or aryl with the proviso that when [ isostere ] is ## str11 ## or [ chohchohchohco ], y is absent ; w is cad , cah , dfcys , dfkcys , dfsta , dfksta , asta , acys or ## str12 ## wherein u is absent , aem , mba , ## str13 ## nhch 2 ph , nhc 4 h 9 , nhch 3 or ## str14 ## with the proviso that when w is cad , cah or nhchch ( oh ) ch 2 ch ( oh ) r 10 , u is absent . other compounds of the instant invention are those of formula i wherein a is hydrogen , boc , z , iva , nva , or ## str15 ## wherein r 2 and r 3 are each independently h , a straight or branched lower alkyl , or r 2 and r 3 when taken together with the nitrogen to which they are attached form a saturated 5 - or 6 - membered ring which may optionally contain an additional heteroatom : o , s , or nr 3 , r 1 is ch 2 ph , ## str16 ## [ isostere ] is [ chohch 2 ], [ coch 2 ], [ chohchoh ], [ ch ( nh 2 ) ch 2 ], ch ═ ch ], ## str17 ## [ ch 2 nh ], [ ch 2 noh ], [ ch 2 s ], [ ch 2 so ], ch 2 so 2 ], [ ch 2 ch 2 ], or [ ch 2 o ]; y is ## str18 ## wherein r 5 is lower alkyl , lower alkenyl , lower alkynyl , arylmethyl or heterocyclicmethyl ; w is cad , cah , dfcys , dfkcys , dfsta , dfksta , asta , acys or ## str19 ## wherein r 10 is lower alkyl or alkenyl ; and u is absent , aem , mba , ## str20 ## nhch 2 ph , nhc 4 h 9 , nhch 3 or ## str21 ## with the proviso that when w is cad , cah or nhchch ( oh ) ch 2 ch ( oh ) r 10 , u is absent . preferred compounds of the instant invention are those of formula i wherein r 1 is ch 2 ph , ## str23 ## [ isostere ] is [ chohch 2 ], [ coch 2 ], [ ch 2 nh ], chohch ═ chco ], [ chohch ═ c ( ch 3 ) co ], chohch ═ c ( c 4 h 9 ) co ], [ chohch ═ c ( ch 2 ph ) co ], or ## str24 ## with the proviso that y is absent when [ isosterel ] is [ chohch ═ chco ], [ chohch ═ c ( c 4 h 9 ) co ], [ chohch ═ c ( ch 3 ) co ], chohch ═ c ( ch 2 ph ) co ], or ## str25 ## y is ## str26 ## wherein r 5 is hydrogen , och 3 , oc 3 h 7 , och 2 ch ═ ch 2 , och 2 c ═ ch , sch 3 , sc 3 h 7 , sch 2 ch ═ ch 2 , sch 2 c ═ ch , nh 2 , nhch 3 , n ( ch 3 ) 2 , ## str27 ## or nhcoch 3 ; u is absent , aem , nhc 4 h 9 , ## str29 ## with the proviso that u is absent when w is cad , cah , or ## str30 ## other preferred compounds of the instant invention are those of formula i wherein y is ## str31 ## wherein r 5 is ch 3 , c 4 h 9 , ch 2 ch ═ ch 2 , ch 2 c ═ ch , ch 2 ph , ## str32 ## most preferred compounds of the instant invention include but are not limited to : ## str33 ## still other valuable compounds falling within the scope of the invention are : ## str34 ## the compounds include solvates and hydrates and pharmaceutically acceptable acid addition salts of the basic compounds of formula i above . the term pharmaceutically acceptable acid addition salt is intended to mean a relatively nontoxic acid addition salt either from inorganic or organic acids such as , for example , hydrochloric , hydrobromic , hydroiodic , sulfuric , phosphoric , acetic , citric , oxalic , malonic , salicylic , malic , benzoic , gluconic , fumaric , succinic , ascorbic , maleic , tartaric , methanesulfonic , and the like . the salts are prepared by contacting the free base form with a sufficient amount of the desired acid to produce a salt in the conventional manner . the free base forms may be regenerated by treating the salt form with a base . the modified peptides of the present invention possess one or more chiral centers and each center may exist in the r ( d ) or s ( l ) configuration . the present invention includes all enantiomeric and epimeric forms as well as the appropriate mixtures thereof . unless otherwise specified the l form is the preferred embodiment . the term lower alkyl refers to straight or branched chain alkyl radicals containing from one to six carbon atoms including but not limited to methyl , ethyl , n - propyl , isopropyl , n - butyl , iso - butyl , sec - butyl , 2 - methylhexyl , n - pentyl , 1 - methylbutyl , 2 , 2 - dimethylbutyl , 2 - methylpentyl , 2 , 2 - dimethylpropyl , n - hexyl , and the like . the preferred lower alkyl groups are methyl , ethyl , n - butyl , and isobutyl . the term arylmethyl refers to a radical of the formula - ch 2 ar where ar can be phenyl , a phenyl substituted with oh , och 3 , or halogen , or 1 - or 2 - naphthyl . the preferred groups are those where aryl is phenyl or p - methoxyphenyl . the term saturated ring containing from two to five carbon atoms , which ring can optionally contain an additional o , s , or nr 3 is meant to include , for example , ## str37 ## the term lower alkenyl refers to straight or branched chain alkenyl radicals containing two to six carbon atoms . the preferred groups are allyl and methylallyl . the term lower alkynyl refers to straight or branched chain alkynyl radicals containing two to six carbon atoms . the preferred groups are -- ch 2 c ═ ch and -- ch 2 c ═ c -- ch 3 . the term heterocyclicmethyl refers to a radical of the formula -- ch 2 - heterocycle , where the heterocycle can be a saturated or unsaturated five or six membered ring containing one or more heteroatoms selected from n , s , and o , and may be optionally substituted with oh , nh 2 , or nr 2 r 3 where r 2 and r 3 have the designation previously described . the preferred radicals embodied in this description are ## str38 ## and the regioisomers thereof . the term isostere means that the atoms enclosed in brackets replace the normal amide bond of the peptitde . the symbol ψ means that the following atoms in brackets constitute an isostere . heteroaryl means a substituted or unsubstituted aromatic ring containing at least one heteroatom selected from o , s , and n and from three to five carbon atoms . the preferred heteroaryls are imidazoles , thiazoles , and amino - substituted thiazoles . aryl means phenyl , naphthyl , or other aromatic groups , including mono - or bicyclic , which may be unsubstituted or substituted , especially monosubstituted by f , cl , br , i , cf 3 , oh , or , or r , wherein r is lower alkyl . some of the above novel compounds may be prepared in accordance with well - known procedures for preparing peptides from their constituent amino acids . other of the novel compounds of the present invention are prepared by a step - wise procedure or by a fragment coupling procedure depending upon the particular final product desired . the following schemes illustrate novel methods of preparing certain compounds of the present invention . ## str39 ## according to scheme i above , the o , n - dimethyl amide of smo - phe ( 1 ) is reacted with the grignard reagent ( 2 ) prepared from 4 - bromo - 1 - propene to give the ketomethylene isostere ( 3 ). the reaction takes place in an inert solvent such as et 2 o or thf at temperatures ranging from - 40 ° to 25 °. reduction gives the hydroxyethylene isostere ( 4 ). this reaction can be carried out with reducing agents such as libh 4 , nabh 4 , kbh 4 , or lialh 4 in an inert solvent such as et 2 o , or thf . for nabh 4 or kbh 4 , the reaction can also be carried out in meoh or aqueous meoh . in addition to the reduction , selection of a specific reducing agent mentioned above leads to different ratios of diastereomers formed in the reduction . thus , one can select the reducing agent to give higher ratios of the desired diastereomer . protection of the hydroxyl group with t - butyldimethylsilyl chloride gives ( 5 ). this reaction is carried out in dmf using imidazole as the base . the reaction is carried out at room temperature for 12 to 40 hours . oxidation of the double bond gives ( 6 ). this reaction is carried out in aqueous acetone using ruo 2 · xh 2 o and naio 4 at 0 ° to 25 ° for one to four hours . compound ( 7 ) is prepared using standard peptide coupling methods . the preferred method is using dcc in the presence of hobt in an inert solvent such as ch 2 cl 2 , dmf , or thf . the reaction is carried out at 0 ° to 25 ° for 8 to 40 hours . removal of the protecting group to give compound ( 8 ) is carried out using tetrabutylammonium fluoride . this reaction is carried out in thf at room temperature for periods of 4 to 12 hours . it will be evident to one skilled in the art that this series of reactions can be carried out with other compounds that contain the fragment ψ [ chohch 2 ] ch 2 ch ═ ch 2 . ## str40 ## according to scheme ii above , the aldehyde ( 1 ) is reacted with methyltriphenylphosphonium bromide in an inert solvent such as thf using a base such as n - butyl lithium . the reaction can be carried out from - 80 ° to 0 ° for two to 24 hours and leads to ( 2 ). when ( 2 ) is treated with ethyl chlorooximinoacetate in an inert solvent such as et 2 o or thf and then treated slowly via a syringe pump with an organic base such as et 3 n over a period of 8 to 24 hours there is obtained ( 3 ). hydrolysis of ( 3 ) to give ( 4 ) can be carried out with alkali metal bases such as naoh , koh , or lioh in aqueous meoh , etoh , or acetone at room temperature for periods of 1 to 4 hours . standard peptide coupling methods can be used to prepare ( 5 ). the preferred method is using dcc in the presence of hobt in an inert solvent such as ch 2 cl 2 , thf , or dmf at room temperature for 12 to 40 hours . catalytic reduction of ( 5 ) gives ( 6 ). this reaction can be carried out using raney nickel catalyst in the presence of boric acid and hydrogen gas . the preferred solvents are meoh , etoh , or 2 - propanol . the reaction is carried out at 40 to 75 psi for 2 to 8 hours . the effectiveness of the aforementioned compounds is determined by a test for in vitro renin inhibitory activity . this activity is determined by a standard radioimmunoassay for angiotensin i . ln this assay the enzyme , renin , incubated for 2 hours at 37 ° in the presence of a substrate , angiotensinogen , generates the product , angiotensin i . test compounds are added to the incubation mixture . relative activity is reported as the percent inhibition at the specified molar concentration or as the ic 50 , which is the molar concentration of test compound causing a 50 % inhibition of the renin activity . table ii______________________________________compound in vitro activity______________________________________smopheψ [ chohchchco ] cad 2 . 5 × 10 . sup .- 8 * bocpheψ [ chch ] glycad 1 % @ 3 × 10 . sup .- 8 ## str41 ## 21 % @ 1 × 10 . sup .- 8smopheψ [ coch . sub . 2 ] glycad 8 . 7 × 10 . sup .- 8 * smopheψ [ chohch . sub . 2 ] glycad 2 . 3 × 10 . sup .- 9 *( isomer a ) smopheψ [ chohch . sub . 2 ] glycad 1 . 7 × 10 . sup .- 8 *( isomer b ) zpheψ [ coch . sub . 2 ] glycad 1 % @ 1 × 10 . sup .- 8zpheψ [ chohch . sub . 2 ] glycad 2 . 4 × 10 . sup .- 7 *( mixture of diastereomers ) zpheψ [ chohch . sub . 2 ] glycad 2 . 0 × 10 . sup .- 7 *( slow eluting diastereomer ) pheψ [ chohch . sub . 2 ] glycad 28 % @ 1 × 10 . sup .- 6bocpheψ [ chohch . sub . 2 ] glycad 3 . 0 × 10 . sup .- 8 *( mixture of diastereomers ) bocpheψ [ chohch . sub . 2 ] glycad 1 . 5 × 10 . sup .- 8 *( slow eluting diastereomer ) smopheψ [ ch . sub . 2 nh ] glycad 2 . 6 × 10 . sup .- 6 * ## str42 ## 45 % @ 10 . sup .- 6 ( isomer a ) ## str43 ## 26 % @ 10 . sup .- 6 ( isomer b ) ______________________________________ * ic . sub . 50 as can be seen from the above table , compounds of the present invention have a significant effect on the activity of renin and thus are useful for the treatment of hypertension , hyperaldosteronism , glaucoma , and congestive heart failure . they are also useful as agents for treatment of diseases caused by htlv - i , ii , iii viruses . the compounds of the instant invention , when tested by measuring the effect on intraocular pressure in rabbits as described by tinjum , a . m ., acta ophthamologica , 50 , 677 ( 1972 ), are expected to exhibit antiglaucoma activity . for preparing pharmaceutical compositions from the compounds described by this invention , inert , pharmaceutically acceptable carriers can be either solid or liquid . solid form preparations include powders , tablets , dispersible granules , capsules , cachets , and suppositories . a solid carrier can be one or more substances which may also act as diluents , favoring agents , solubilizers , lubricants , suspending agents , binders , or tablet disintegrating agents ; it can also be encapsulating material . in powders , the carrier is a finely divided active compound . in the tablet the active compound is mixed with carrier having the necessary binding properties in suitable proportions and compacted in the shape and size desired . the powder and tablets preferably contain from 5 to 10 to about 70 percent of the active ingredient . suitable solid carriers are magnesium carbonate , magnesium stearate , talc , sugar , tragacanth , methylcellulose , a low melting wax , cocoa butter , and the like . the term &# 34 ; preparation &# 34 ; is intended to include the formulation of the active compound with encapsulating material as carrier providing a capsule in which the active component ( with or without other carriers ) is surrounded by carrier , which is thus in association with it . similarly , cachets are included . tablets , powders , cachets , and capsules can be used as solid dosage forms suitable for oral administration . the compounds of the present invention may be administered orally , buccally , parenterally , by inhalation spray , rectally , or topically in dosage unit formulations containing conventional nontoxic pharmaceutically acceptable carriers , adjuvants and vehicles as desired . the term parenteral as used herein includes subcutaneous injections , intravenous , intramuscular , intrasternal injection , or infusion techniques . for preparing suppositories , a low melting wax such as a mixture of fatty acid glycerides or cocoa butter is first melted , and the active ingredient is dispersed homogeneously therein by stirring . the molten homogeneous mixture is then poured into convenient sized molds , allowed to cool , and thereby solidify . liquid form preparations include solutions , suspensions , and emulsions . as an example may be mentioned water or water / propylene glycol solutions for parenteral injection . liquid preparations can also be formulated in solution in aqueous polyethylene glycol solution . aqueous suspensions suitable for oral use can be made by dispersing the finely divided active component in water with viscous material , i . e ., natural or synthetic gums , resins , methylcellulose , sodium carboxymethylcellulose , and other well - known suspending agents . also included are solid form preparations which are intended to be converted , shortly before use , to liquid form preparations for either oral or parenteral administration . such liquid forms include solutions , suspensions , and emulsions . these particular solid form preparations are most conveniently provided in unit dosage form and as such are used to provide a single liquid dosage unit . alternately , sufficient solid may be provided so that after conversion to liquid form , multiple individual liquid doses may be obtained by measuring predetermined volumes of the liquid form preparation as with a syringe , teaspoon , or other volumetric container when multiple liquid doses are so prepared , it is preferred to maintain the unused portion of said liquid doses at low temperature ( i . e ., under refrigeration ) in order to retard possible decomposition . the solid form preparations intended to be converted to liquid form may contain , in addition to the active material , flavorants , colorants , stabilizers , buffers , artificial and natural sweeteners , dispersants , thickeners , solubilizing agents , and the like . the liquid utilized for preparing the liquid form preparation may be water , isotonic water , ethanol , glycerin , propylene glycol , and the like , as well as mixtures thereof . naturally , the liquid utilized will be chosen with regard to the route of administration , for example , liquid preparations containing large amounts of ethanol are not suitable for parenteral use . preferably , the pharmaceutical preparation is in unit dosage form . in such form , the preparation is subdivided into unit doses containing appropriate quantities of the active component . the unit dosage form can be a packaged preparation , the package containing discrete quantities of preparation , for example , packeted tablets , capsules , and powders in vials or ampules . the unit dosage form can also be a capsule , cachet , or tablet itself , or it can be the appropriate number of any of these in packaged form . the quantity of active compound in a unit dose of preparation may be varied or adjusted from 1 mg to 500 mg , preferably 5 to 100 mg according to the particular application and the potency of the active ingredient . the composition can , if desired , also contain other compatible therapeutic agents . in therapeutic use as renin inhibitors , the mammalian dosage range for a 70 kg subject is from 1 to 1500 mg / kg of body weight per day or preferably 25 to 750 mg / kg of body weight per day optionally in divided portions . the dosages , however , may be varied depending upon the requirements of the patient , the severity of the condition being treated , and the compound being employed . determination of the proper dosage for a particular situation is within the skill of the art . generally , treatment is initiated with small dosages which are less than the optimum dose of the compound . thereafter the dosage is increased by small increments until the optimum effect under the circumstances is reached . for convenience , the total daily dosage may be divided and administered in portions during the day , if desired . in therapeutic use as an antiglaucoma agent , the compound may also be administered as a topical corneal application of a solution containing the compound in amounts as known to one skilled in the treatment . the present invention includes combinations of novel renin - inhibiting compounds of formula i with one or more antihypertensive agents selected from the group consisting of diuretics , α - and / or β - adrenergic blocking agents , calcium channel blocking agents , central nervous system - acting agents , adrenergic neuron blocking agents , vasodilators , angiotensin converting enzyme inhibitors , and other antihypertensive agents . the following examples are provided to enable one skilled in the art to practice the present invention . these examples are not intended in any way to limit the scope of the invention but are illustrative thereof . a solution of 740 mg ( 2 . 0 mmole ) of ## str44 ## 270 mg ( 2 . 0 mmole ) of hobt , and 560 mg ( 2 . 0 mmole ) of cad hc ( ep - 229 , 667 ) in 15 ml dmf was cooled in ice and 0 . 3 ml ( 2 . 0 mmole ) of et 3 n added , followed by a solution of 420 mg ( 2 . 0 mmole ) of dcc in 5 ml dmf . after stirring for 15 minutes at 0 °, the mixture was allowed to stir at room temperature overnight . the mixture was filtered and the dmf removed under high vacuum . the residue was taken up in etoac , filtered , and washed with 1 n hcl , h 2 o , saturated nahco 3 , and saturated nacl . drying over mgso 4 and removal of the solvent under reduced pressure gave 1 . 1 g of the crude product as a tan solid . chromatography on silica gel , eluting with chcl 3 / meoh ( 96 / 4 ) gave the product . recrystallization from etoac / hexane gave 487 mg of the product as a white solid . the structure was confirmed by mass spectroscopy . calcd . for c 30 h 49 n 3 o 7 s ( mw 595 . 72 ): c , 60 . 48 ; h , 8 . 29 ; n , 7 . 05 . a solution of 1 . 55 g ( 5 . 1 mmole ) of [ s -( e )]- 5 -[[( 1 , 1 - dimethylethoxy ) carbonyl ] amino ]- 6 - phenyl - 3 - hexenoic acid ( j . chem . soc . 799 ( 1980 )), 686 mg ( 5 . 1 mmole ) of hobt , and 1 . 43 g ( 5 . 1 mmole ) of cad · hcl in 25 ml dmf was cooled in ice and treated with a solution of 1 . 05 g ( 5 . 1 mmole ) of dcc in 10 ml dmf followed by 0 . 71 ml ( 5 . 1 mmole ) of et 3 n . after 15 minutes at 0 °, the mixture was allowed to stir at room temperature overnight . the mixture was filtered and the solvent removed under high vacuum . the residue was taken up in etoac , filtered , and washed with 1n hcl , h 2 o , saturated nahco 3 , and saturated nacl . drying over mgso 4 and removal of the solvent under reduced pressure left 2 . 7 g of the crude product . chromatography on silica gel , eluting with chcl 3 / meoh ( 98 / 2 ) gave 2 . 4 g of the product as a white solid . the structure was confirmed by nmr and mass spectroscopy . calcd . for c 31 h 50 n 2 o 5 · 0 . 1chcl 3 ( mw 542 . 66 ): c , 68 . 83 ; h , 9 . 31 ; n , 5 . 16 . a solution of 0 . 5 g ( 0 . 94 mmole ) of smo - pheψ [ e - ch ═ ch ] gly - cad in 10 ml ch 2 cl 2 was treated with 291 mg ( 1 . 43 mmole ) of m - chloroperbenzoic acid and allowed to stir at room temperature for three days . the solvent was removed under reduced pressure and the residue taken up in etoac and washed with 5 % nahso 3 , h 2 o , saturated nahco 3 , and saturated nacl . drying over mgso 4 and removal of the solvent under reduced pressure gave 490 mg of the crude product . chromatography on silica gel , eluting with chcl 3 / meoh ( 98 / 2 ) gave 220 mg of the product as a white foam . the structure was confirmed by nmr and mass spectroscopy . calcd . for c 31 h 50 n 2 o 6 · 0 . 15 chcl 3 ( mw 564 . 63 ): c , 66 . 26 ; h , 8 . 95 ; n , 4 . 96 . a solution of 1 . 6 g ( 4 . 32 mmole ) of smo - pheψ [ coch 2 ] gly and 0 . 6 g ( 4 . 4 mmole ) of hobt in 75 ml ch 2 cl 2 and 5 ml dmf was cooled in ice and treated with 0 . 91 g ( 4 . 4 mmole ) of dcc , followed by a solution of 1 . 05 g ( 4 . 32 mmole ) of cad in 25 ml ch 2 cl 2 / dmf ( 1 / 1 ). after stirring at room temperature overnight , the mixture was filtered and the solvent removed under reduced pressure . the residue was taken up in et 2 o and washed with 1n citric acid , saturated nacl , saturated nahco 3 , and saturated nacl . after drying over mgso 4 , the product was precipitated by the addition of hexane to the et 2 o solution . there was obtained 1 . 55 g of the product . the structure was confirmed by nmr and mass spectroscopy . calcd . for c 30 h 49 n 3 o 7 s · 0 . 3 h 2 o ( mw 601 . 21 ): c , 59 . 93 ; h , 8 . 31 ; n , 6 . 99 . a solution of 2 . 58 g ( 3 . 62 mmole ) of smo - pheψ [ ch ( otbdms ) ch 2 ] gly - cad , isomer a , in 70 ml of a 1m solution of tetrabutylammonium fluoride in thf was stirred at room temperature for six hours . the solvent was removed under reduced pressure to give an oil . this was taken up in etoac and washed three times with 1n hcl , three times with saturated nahco 3 , then with saturated nacl . drying over mgso 4 and removal of the solvent under reduced pressure gave 2 . 13 g of the crude product . recrystallization from ch 2 cl 2 / et 2 o gave 1 . 59 g of the product as a white solid . the structure was confirmed by nmr and mass spectroscopy . calcd . for c 30 h 51 n 3 o 7 s · 0 . 5 h 2 o ( mw 606 . 83 ): c , 59 . 38 ; h , 8 . 64 ; n , 6 . 92 . in a manner similar to that of example 5 , 2 . 55 g ( 3 . 58 mmole ) of smo - pheψ [ ch ( otbdms ) ch 2 ] gly - cad , lsomer b , gave 0 . 75 g of the product as a pale yellow solid . the structure was confirmed by nmr and mass spectroscopy . calcd . for c 30 h 51 n 3 o 7 s · 0 . 25h 2 o ( mw 602 . 32 ): c , 59 . 82 ; h , 8 . 62 ; n , 6 . 98 . a solution of 1 . 1 g ( 2 . 45 mmole ) of pheψ [ chohch 2 gly - cad ( mixture of diastereomers , example 11 ) and 0 . 47 g ( 2 . 7 mmole ) of morpholinosulfamyl chloride ( prepared according to the method of r . wegler and k . bodenbenner , ann 624 , 25 ( 1959 )) in 50 ml dmf was treated with 0 . 38 ml ( 2 . 7 mmole ) of et 3 n and stirred at room temperature for four days . the solvent was removed under reduced pressure and the residue suspended in etoac . this was washed with 1 n citric acid , saturated nahco 3 , and saturated nacl . drying over mgso 4 and removal of the solvent under reduced pressure gave 1 . 51 g of the crude product . chromatography on silica gel , eluting with a gradient of 2 %- 15 % meoh in chcl 3 gave the product . trituration with et 2 o gave 0 . 76 g of the product as a white solid . the structure was confirmed by nmr and mass spectroscopy . calcd . for c 30 h 51 n 3 o 7 s · 0 . 25 h 2 o ( mw 602 . 32 ): c , 59 . 82 ; h , 8 . 62 ; n , 6 . 97 . a solution of 10 . 1 g ( 28 . 4 mmole ) of z - pheψ [ coch 2 ] gly and 3 . 92 g ( 28 . 9 mmole ) of hobt in 150 ml ch 2 cl 2 and 60 ml dmf was cooled in ice and 5 . 98 g ( 28 . 9 mmole ) of dcc added , followed by a solution of 7 . 95 g ( 28 . 4 mmole ) of cad · hcl and 4 . 04 ml ( 28 . 9 mmole ) of et 2 n in 150 ml of cold ch 2 cl 2 . after stirring at room temperature overnight , the mixture was filtered , and the filtrate evaporated to an oil . this was taken up in et 2 o and washed with 1n citric acid , saturated nacl , saturated nahco 3 , and saturated nacl . drying over mgso 4 and removal of the solvent under reduced pressure left a solid . recrystallization from chcl 3 / et 2 o gave 11 . 03 g of the product . the structure was confirmed by nmr and mass spectroscopy . calcd . for c 34 h 48 n 2 o 6 ( mw 580 . 77 ): c , 70 . 32 ; h , 8 . 33 ; n , 4 . 82 . a suspension of 9 . 08 g ( 15 . 63 mmole ) of z - pheψ [ coch 2 gly - cad ( example 8 ) in 250 ml absolute etoh was warmed to 40 ° to effect solution , and 25 ml of h 2 o was then added , followed by 3 . 37 g ( 62 . 5 mmole ) of kbh 4 . after stirring at room temperature for 1 . 5 hours , the suspension was filtered , and 25 ml acetone added , followed by 5 ml of hoac . the solvent was removed under reduced pressure and the residue mixed with 200 ml of h 2 o , giving a solid . this was collected , then suspended in warm chcl 3 . a solid was filtered off , and the filtrate washed with 1n citric acid , saturated nacl , saturated nahco 3 , and saturated nacl . drying over mgso 4 and removal of the solvent under reduced pressure left a solid . trituration with et 2 o gave 4 . 11 g of the product as a white solid . thin layer showed this to be a mixture of fast and slow running diastereomers . the structure was confirmed by nmr and mass spectroscopy . calcd . for c 34 h 50 n 2 o 6 ( mw 582 . 79 ): c , 70 . 07 ; h , 8 . 65 ; n , 4 . 81 . the chcl 2 - insoluble solid from example 9 was dissolved in a large volume of hot chcl 3 , and while hot , washed with 1n citric acid , saturated nacl , saturated nahco 3 , and saturated nacl . the hot solution was dried over mgso 4 and then concentrated to a small volume . addition of et 2 o gave 3 . 13 g of the product as a white solid . thin layer showed this to be the slow running diastereomer . the structure was confirmed by nmr and mass spectroscopy . calcd . for c 34 h 50 n 2 o 6 ( mw 582 . 79 ): c , 70 . 07 ; h , 8 . 65 ; n , 4 . 81 . a solution of 3 . 72 g ( 6 . 38 mmole ) of z - pheψ [ chohch 2 ] gly - cad ( mixture of diastereomers , example 9 ) in 100 ml meoh was treated with 370 mg of 20 % pd / c and purged with hydrogen for three hours . the suspension was filtered and the solvent removed under reduced pressure , leaving 2 . 77 g of the crude product . chromatography on silica gel , eluting with a gradient of 0 %- 5 % meoh in chcl 3 gave 2 . 61 g of the product as a solid . the structure was confirmed by nmr and mass spectroscopy . calcd . for c 26 h 44 n 2 o 4 ( mw 448 . 65 ): c , 69 . 60 ; h , 9 . 88 ; n , 6 . 24 . a solution of 2 . 79 g ( 4 . 79 mmole ) of z - pheψ [ chohch 2 gly - cad ( slow isomer , example 10 ) in 100 ml meoh was treated with 350 mg of 20 % pd / c and purged with hydrogen for three hours . the suspension was filtered and the solvent removed under reduced pressure , leaving 2 . 09 g of the product as a white foam . the structure was confirmed by nmr and mass spectroscopy . calcd . for c 26 h 44 n 2 o 4 · 0 . 5meoh ( mw 464 . 67 ): c , 68 . 49 ; h , 9 . 98 ; n , 6 . 03 . a solution of 1 . 25 g ( 2 . 79 mmole ) of pheψ [ chohch 2 ] gly - cad ( mixture of diastereomers , example 11 ) and 0 . 67 g ( 3 . 07 mmole ) of di - t - butyldicarbonate in 50 ml thf was stirred at room temperature overnight . the solvent was removed under reduced pressure and the residue triturated with et 2 o to give 1 . 15 g of crude product . chromatography on silica gel , eluting with chcl 3 / meoh ( 9 / 1 ) gave 0 . 93 g of the product as a white solid . the structure was confirmed by nmr and mass spectroscopy . calcd . for c 31 h 52 n 2 o 6 · 0 . 05 chcl 3 ( mw 555 . 54 ): c , 67 . 13 ; h , 9 . 44 ; n , 5 . 04 . in a manner similar to that described for example 13 , 1 . 25 g ( 2 . 79 mmole ) of pheψ [ chohch 2 ] gly - cad ( slow isomer , example 12 ) gave 0 . 84 g of product as a white solid . the structure was confirmed by nmr and mass spectroscopy . calcd . for c 31 h 52 n 2 o 6 ( mw 548 . 77 ): c , 67 . 85 ; h , 9 . 55 ; n , 5 . 10 . a solution of 3 . 1 g ( 10 . 4 mmole ) of smo - phe [ cho ] and 3 . 15 g ( 10 . 5 mmole ) of gly - cad in 250 ml absolute etoh was treated with 16 g of activated 3a molecular sieves followed by 0 . 72 g ( 11 . 5 mmole ) of nacnbh 3 and a trace of bromocresol green . the blue solution was gradually acidified with hcl gas in etoh over one hour , until the solution remained green . after stirring at room temperature for three days the mixture was filtered and evaporated to a foam . this was taken up in etoac and washed with 1n hcl , saturated nacl , saturated nahco 3 , and saturated nacl . drying over mgso 4 and removal of the solvent under reduced pressure gave 5 . 77 g of the crude product . chromatography on silica gel , eluting with etoac / chcl 3 ( 1 / 1 ) gave 3 . 0 g of a white foam . this was rechromatographed on silica gel , eluting with a gradient of 0 %- 3 % meoh in chcl 3 to give 2 . 81 g of the product as a white foam . the structure was confirmed by nmr and mass spectroscopy . calcd . for c 29 h 50 n 4 o 6 s · 0 . 05chcl 3 · 0 . 25h 2 o ( mw 593 . 28 ): c , 58 . 81 ; h , 8 . 59 ; n , 9 . 44 . to a solution of 3 . 82 g ( 6 . 82 mmole ) of ## str46 ## and 0 . 84 g ( 13 . 65 mmole ) of boric acid in 250 ml of 10 % aqueous meoh was added 0 . 5 g of raney nickel and the suspension shaken under an atmosphere of hydrogen at 53 psi for four hours . the catalyst was removed by filtration through celite and the filtrate concentrated under reduced pressure to a volume of approximately 50 ml . the concentrated filtrate was diluted with ethyl acetate and extracted three times with brine . the organic phase was dried over mgso 4 , filtered , and the solvent removed under reduced pressure to give 3 . 84 g of a diastereomeric mixture of the products . these were separated by flash chromatography using a gradient of 2 %- 10 % meoh in ch 2 c 2 . after the initial elution of boc - pheψ [ chohch 2 ] coco - cad , continued elution gave 1 . 02 g of the product , isomer a , which was purified by recrystallization from et 2 o . the structure was confirmed by nmr and mass spectroscopy . calcd . for c 31 h 53 n 3 o 6 ( mw 563 . 77 ): c , 66 . 04 ; h , 9 . 48 ; n , 7 . 45 . continued elution from the column gave 0 . 79 g of the product , isomer b , which was purified by recrystallization from etoac / hexane . the structure was confirmed by nmr and mass spectroscopy . calcd . for c 31 h 53 n 3 o 6 ( mw 563 . 77 ): c , 66 . 04 ; h , 9 . 48 ; n , 7 . 45 . a solution of 0 . 99 g ( 1 . 66 mmole ) of smo - pheψ [ coch 2 ] gly - cad , ( example 4 ) and 9 . 7 g ( 0 . 126 mole ) of nh & lt ; oac in 30 ml meoh was treated with 20 g of activated 3a molecular sieves . this was then treated with 0 . 32 g ( 3 . 32 mmole ) of nacnbh 3 and the mixture left stirring at room temperature overnight . the mixture was then filtered and the solvent removed under reduced pressure . the residue was taken up in etoac and washed with h 2 o , 1 n citric acid , saturated nacl , saturated nahco 3 , and saturated nacl . drying over mgso 4 and removal of the solvent under reduced pressure left 0 . 68 g of the crude product . this was taken up in etoac / et 2 o , filtered , and the filtrate treated with hcl gas . the precipitated solid was collected and washed with et 2 o to give 0 . 59 g of the product as a yellow solid . the structure was confirmed by nmr and mass spectroscopy . calcd . for c 30 h 52 n 4 o 6 s · hcl ( mw 633 . 21 ): c , 56 . 90 ; h , 8 . 44 ; n , 8 . 85 . under nitrogen , a suspension of 50 . 9 g ( 0 . 11 mole ) of 1 - trimethysilylpropyne - 3 - triphenylphosphonium bromide ( j . chem . soc . perkin i , 307 ( 1982 )) in 500 ml thf was cooled to - 80 ° and 70 ml ( 0 . 11 mole ) of a 1 . 6 m solution of n - butyl lithium in hexane was added slowly via a syringe . the dark red - brown suspension was stirred at - 80 ° for 1 . 5 hours after the addition was complete . this was then treated dropwise with a solution of 16 . 7 g ( 0 . 056 mole ) of smo - phe [ cho ] in 500 ml thf . after one hour at - 80 °, the mixture was left at room temperature overnight . the solvent was removed under reduced pressure and the residue taken up in etoac and washed with 1 n citric acid , h 2 o , saturated nahco 3 , and saturated nacl . drying over mgso 4 and removal of the solvent under reduced pressure left 44 . 3 g of a dark oil . chromatography on silica gel , eluting with chcl 3 gave 11 . 6 g of product . recrystallization from et 2 o / hexane gave 7 . 8 g of pure product , mp 128 ° - 130 °. the nmr confirmed this as the e - isomer ( j = 16 h 2 ). ## str48 ## under nitrogen , 70 ml ( 0 . 07 mole ) of a 1 m solution of bh 3 in thf was cooled in ice and treated dropwise with a solution of 14 . 1 ml ( 0 . 139 mole ) of cyclohexene in 150 ml thf . after the addition was complete , the mixture was stirred at 0 ° for one hour . the suspension was then treated with a solution of 7 . 78 g ( 0 . 02 mole ) of ## str49 ## in 25 ml thf . after stirring at 0 ° for one hour , the mixture was treated dropwise with 26 ml meoh , 36 ml 2 n naoh , and then with 24 ml of 30 % h 2 o 2 , keeping the temperature below 18 °. after stirring at 0 ° for 20 minutes , the mixture was allowed to stir at room temperature for one hour . this was poured into 500 m h 2 o containing 27 ml of 2 n naoh . after extracting three times with et 2 o , the ph was brought to 2 . 0 with di . hcl , and the solution extracted three times with et 2 o . the combined et 2 o phases were washed with saturated nacl , dried over mgso 4 , and the solvent removed under reduced pressure leaving 6 . 3 g of the product or a viscous oil . the structure was confirmed by nmr and mass spectroscopy . ## str50 ## a solution of 5 . 3 g ( 0 . 015 mole ) of ## str51 ## in 40 ml thf was cooled in ice and 2 . 76 g ( 0 . 017 mole ) of cdi added . the solution was stirred at room temperature for 0 . 5 hours , diluted with 150 ml meoh , and stirred at room temperature overnight . the solvent was removed under reduced pressure and the residue taken up in et 2 o , washed two times with 1 n hcl , h 2 o , two times with saturated nahco 3 , and then with saturated nacl . drying over mgso 4 and removal of the solvent under reduced pressure left 4 . 37 g of a yellow solid . chromatography on silica gel , eluting with chcl 3 / meoh ( 98 / 2 ) gave 3 . 8 g of an oil which solidified on standing . recrystallization from meoh / h 2 o gave 3 . 37 g of the product as a white solid , mp 80 °- 81 °. the structure was confirmed by nmr and mass spectroscopy . ## str52 ## a solution of 3 . 37 g ( 9 . 1 mmole ) of ## str53 ## in 40 ml ch 2 c 2 was treated with 3 . 0 g ( 13 . 7 mmole ) of m - chloroperbenzoic acid and stirred at room temperature overnight . the mixture was filtered and the solvent removed under reduced pressure . the residue was taken up in etoac and washed twice with 5 % na 2 so 3 , h 2 o , saturated nahco 3 , and then with saturated nacl . drying over mgso 4 and removal of the solvent under reduced pressure left 3 . 36 g of the crude product . since nmr showed some double bond still present , the material was resubjected to the oxidation conditions . using the same workup as before gave 3 . 2 g of the crude product as an oil . chromatography on silica gel , eluting with chcl 3 / meoh ( 99 / 1 ) gave 1 . 53 g of the product as an oil . the material was used directly in the next step . ## str54 ## a solution of 1 . 53 g ( 4 . 0 mmole ) of ## str55 ## in 20 ml meoh was treated with 15 ml ( 15 mmole ) of 1 n naoh and stirred at room temperature for two hours . the solvent was removed under reduced pressure and the residue taken up in h 2 o and washed twice with et 2 o . the ph was brought to 2 . 1 with dilute hcl and the solution extracted twice with chcl 3 . the chcl 3 was washed with saturated nacl , dried over mgso 4 , and the solvent removed under reduced pressure , leaving 0 . 75 g of the product as a golden foam . the structure was confirmed by nmr and mass spectroscopy . to a solution of 2 . 33 g ( 6 . 6 mmole ) of smo - pheψ [ coch 2 ] ch 2 ch ═ ch 2 in 140 ml acetone was added a solution of 10 . 6 g ( 49 . 6 mmole ) of naio 4 and 110 mg of ruo 2 · xh 2 o in 60 ml h 2 o . after stirring at room temperature for two hours , 20 ml of 2 - propanol was added , and the mixture filtered through celite . the filtrate was concentrated to an aqueous suspension . this was saturated with solid nahco 3 , filtered , and washed with chcl 3 . the ph was then adjusted to 1 . 0 with conc . hcl , and the mixture extracted with chcl 3 . the chcl 3 extract was washed with a 4 % solution of na 2 so 3 which had been adjusted to ph 2 , then with saturated nacl . after drying over mgso 4 , the solvent was removed under reduced pressure to give 1 . 81 g of the product as a white foam . the structure was confirmed by nmr and mass spectroscopy . under nitrogen , a grignard solution prepared from 5 . 44 g ( 224 mmole ) of mg turnings and 22 . 7 ml ( 224 mmole ) of 4 - bromo - 1 - butene in 350 ml thf was heated to reflux , then cooled to - 5 ° and treated with a suspension of 20 . 0 g ( 55 . 9 mmole ) of smo - phe - n ( ch 3 ) och 3 in 135 ml thf . after stirring at room temperature overnight , the mixture was evaporated to an oil . the oil was poured into a cold , saturated solution of nh 4 cl and extracted with etoac . the etoac was washed with 1 n citric acid , saturated nacl , saturated nahco 3 , and saturated nacl . drying over mgso 4 and removal of the solvent under reduced pressure gave the crude product as an oil . chromatography on silica gel , eluting with hexane / etoac ( 70 / 30 ) gave 16 . 9 g of the product as an oil . the structure was confirmed by nmr and mass spectroscopy . a solution of 6 . 35 g ( 18 . 0 mmole ) of smo - pheψ [ coch 2 ] ch 2 ch ═ ch 2 in 200 ml of absolute etoh was treated with 3 . 89 g ( 72 . 0 mmole ) of kbh 4 followed by 20 ml h 2 o . after stirring at room temperature for 2 . 5 hours , 100 ml of acetone was added and the mixture stirred for 15 minutes . the suspension was filtered and the filtrate evaporated to an oil which solidified . there was obtained 6 . 04 g of the product . the structure was confirmed by nmr and mass spectroscopy . a solution of 5 . 95 g ( 16 . 8 mmole ) of smo - pheψ [ chohch 2 ] ch 2 ch ═ ch 2 in 100 ml thf was treated with 1 . 48 g ( 22 mmole ) of imidazole and 3 . 29 g ( 22 mmole ) of t - butyldimethysilyl chloride and the mixture stirred at room temperature for two days . an additional 0 . 8 g ( 11 . 8 mmole ) of imidazole and 1 . 77 g ( 11 . 7 mmole ) of t - butyldimethylsilyl chloride was then added and the mixture stirred overnight . the solvent was removed under reduced pressure and the residue suspended in etoac / et 2 o ( 1 / 1 ) and washed with h 2 o , 1 n citric acid , saturated nacl , saturated nahco 3 , and saturated nacl . drying over mgso 4 and removal of the solvent under reduced pressure gave the crude product as a mixture of diastereomers . chromatography on silica gel , eluting with a gradient of 0 %- 20 % etoac in hexane gave 3 . 34 g of the faster eluting diastereomer as a glass . the structure was confirmed by nmr and mass spectroscopy . continued elution from the column gave 2 . 86 g of the slower eluting diastereomer as a glass . the structure was confirmed by nmr and mass spectroscopy . a solution of 3 . 04 g ( 6 . 49 mmole ) of smo - pheψ [ ch ( otbdms ) ch 2 ] ch 2 ch ═ ch 2 ( fast isomer ) in 140 ml acetone was treated with a solution of 10 . 4 g ( 48 . 77 mmole ) of naio 4 and 100 mg of ruo 2 · xh 2 o in 60 ml h 2 o and the mixture stirred at 15 ° for two hours . this was then treated with 30 ml of 2 - propanol and the mixture filtered through celite . the filtrate was concentrated to an aqueous suspension . this was saturated with solid nahco 3 , filtered , and extracted with chcl 3 , which carried over the sodium salt . the chcl 3 was extracted with a 4 % solution of na 2 so 3 which had been adjusted to ph 2 , then with saturated nacl . drying over mgso 4 , and removal of the solvent under reduced pressure gave the crude product . this was taken up in et 2 o , filtered , and the solvent removed under reduced pressure to give 1 . 88 g of the product as a white foam . the structure was confirmed by nmr and mass spectroscopy . in a manner similar to that described for isomer a , 2 . 77 g ( 5 . 91 mmole ) of smo - pheψ [ ch ( otbdms ) ch 2 ] ch 2 ch ═ ch 2 ( slow isomer ) gave 1 . 95 g of the product after recrystallization from hexane . the structure was confirmed by nmr and mass spectroscopy . a solution of 1 . 79 g ( 3 . 68 mmole ) of smo - pheψ [ ch ( otbdms ) ch 2 gly , ( isomer a ) and 0 . 51 g ( 3 . 79 mmole ) of hobt in 80 ml ch 2 cl 2 and 5 ml dmf was cooled in ice and treated with 0 . 78 g ( 3 . 79 mmole ) of dcc , then with a solution of 0 . 9 g ( 3 . 68 mmole ) of cad in 25 ml of dmf / ch 2 cl 2 ( 80 / 20 ). after stirring at room temperature overnight , the mixture was filtered and the solvent removed under reduced pressure . the residue was taken up in etoac and washed with 1 n citric acid , saturated nacl , saturated nahco 3 , and saturated nacl . drying over mgso 4 and removal of the solvent under reduced pressure left an oil . this was taken up in et 2 o , filtered to remove insolubles , and evaporated to give 2 . 7 g of the product as a white foam . the structure was confirmed by nmr and mass spectroscopy . in a manner similar to that described for isomer a , 1 . 86 g ( 3 . 82 mmole ) of smo - pheψ [ ch ( otbdms ) ch 2 ] gly , ( isomer b ) gave 2 . 76 g of the product as a white foam . the structure was confirmed by nmr and mass spectroscopy . a solution of 22 . 7 g ( 44 . 37 mmole ) of z - pheψ [ coch 2 ] gly [( co 2 - t - bu ) 2 ], ( u . s . pat . no . 4 , 743 , 585 ), in 150 ml of ch 2 cl 2 was treated with 150 ml of tfa and stirred at room temperature for three hours . the solvent was removed under reduced pressure , and the residue taken up in ch 2 cl 2 and the solvent removed again . this process was then repeated giving a solid . this was taken up in et 2 o , washed with saturated nacl , and then with saturated nahco 3 . the nahco 3 solution was brought to ph 1 and extracted with et 2 o . the et 2 o phase was washed with saturated nacl , dried over mgso 4 , and the solvent removed under reduced pressure , leaving 16 . 25 g of the product as a white foam . the structure was confirmed by nmr and mass spectroscopy . a solution of 15 . 06 g ( 37 . 7 mmole ) of z - pheψ [ coch 2 gly [( co 2 h ) 2 ] in 300 ml toluene was heated at reflux for five hours . the solvent was removed under reduced pressure and the residue taken up in et 2 o . this was washed with 1 n citric acid , saturated nacl , and saturated nahco 3 . the nahco 3 wash was brought to the congo red color change with conc . hcl , then extracted with et 2 o . the et 2 o was washed with saturated nacl and dried over mgso 4 . dilution with hexane caused a solid to precipitate . the mixture was concentrated under reduced pressure , and the solid collected and washed with hexane . there was obtained 10 . 33 g of the product as a white solid . the structure was confirmed by nmr and mass spectroscopy . a solution of 8 . 0 g ( 25 . 4 mmole ) of smo - phe in 100 ml of thf / ch 2 cl 2 ( 1 / 1 ) was cooled to - 40 ° and 4 . 54 g ( 28 mmole ) of carbonyldiimidazole added . the mixture was then kept at - 5 ° for 1 . 5 hours . to this was added a solution of 2 . 73 g ( 28 mmole ) of o , n - dimethylhydroxylamine , hydrochloride , and 3 . 23 ml ( 28 mmole ) of n - methylpiperidine in 40 ml ch 2 c 2 . after stirring at room temperature overnight , the mixture was filtered and the filtrate evaporated . the residue was taken up in etoac and washed with 1 n citric acid , saturated nacl , saturated nahco 3 , and saturated nacl . drying over mgso 4 and removal of the solvent under reduced pressure left 9 . 69 g of the crude product . chromatography on silica gel , eluting with etoac / chcl 3 / meoh ( 49 / 49 / 2 ) gave 7 . 56 g of the product as a syrup which solidified . the structure was confirmed by nmr and mass spectroscopy . a solution of 5 . 0 g ( 14 . 0 mmole ) of smo - phe - n ( ch 3 ) och 3 in 60 ml thf was cooled to - 10 ° and 1 . 09 g ( 28 . 7 mole ) of lithium aluminum hydride added rapidly in portions . after stirring at - 20 ° for 20 minutes , a solution of 6 . 8 g khso 4 in 50 ml h 2 o was added as rapidly as possible while controlling vigorous offgassing . after adjusting the ph to 2 , the mixture was extracted with etoac . the etoac was washed with 1 n hcl , then with saturated nacl . drying over mgso 4 and removal of the solvent under reduced pressure gave a solid . this was triturated with et 2 o to give 3 . 3 g of the product as a white solid . the structure was confirmed by nmr . a solution of 2 . 09 g ( 10 . 0 mmole ) of z - gly and 1 . 37 g ( 10 . 2 mmole ) of hobt in 40 ml ch 2 cl 2 and 6 ml dmf was cooled in ice and 2 . 1 g ( 10 . 2 mmole ) of dcc added , followed by a solution of 2 . 79 g ( 10 . 0 mmole ) of cad · hcl and 1 . 42 ml ( 10 . 3 mmole ) of et 3 n in 40 ml ch 2 cl 2 . after stirring at room temperature overnight , the mixture was filtered and the solvent removed under reduced pressure . the residue was taken up in etoac and washed with 1 n citric acid , saturated nacl , saturated nahco 3 , and saturated nacl . drying over mgso 4 and removal of the solvent under reduced pressure left 2 . 92 g of a solid . two recrystallizations from etoac / et 2 o gave 2 . 63 g of the product as a white solid . the structure was confirmed by nmr and mass spectroscopy . a solution of 9 . 4 g ( 21 . 6 mmole ) of z - gly - cad in 250 ml meoh was treated with 0 . 8 g of 20 % pd / c and purged with hydrogen for three hours . the mixture was filtered and the solvent removed under reduced pressure giving 6 . 6 g of the product as a white foam . the structure was confirmed by nmr and mass spectroscopy . to a cold (- 60 °) suspension of 16 . 0 g ( 44 . 8 mmole ) of methyltriphenylphosphonium bromide in 100 ml dry thf was added dropwise 28 ml ( 44 . 8 mmole ) of a 1 . 6 m solution of n - butyl lithium in hexane over a period of 20 minutes . the reaction mixture was stirred for 15 minutes at - 60 °, followed by the dropwise addition of 10 . 4 g ( 40 . 73 mmole ) of boc - phenylalanal in 100 ml thf over a period of 30 minutes . the mixture was allowed to warm to room temperature , stirred for two hours , then poured into water . the aqueous mixture was extracted three times with et 2 o . the combined et 2 o layers were washed 0 . 5 n hcl , saturated nahco 3 , and brine . drying over mgso 4 and removal of the solvent under reduced pressure gave the crude product . chromatography on silica gel , eluting with a gradient of 10 %- 30 % etoac in hexane gave 9 . 42 g of the product . the structure was confirmed by nmr and mass spectroscopy . ## str57 ## to a solution of 7 . 89 g ( 31 . 90 mmole ) of ## str58 ## in 150 ml of et 2 o was added 10 . 15 g ( 67 mmole ) of ethyl chlorooximinioacetate . to this reaction mixture was added 7 . 10 g ( 70 . 18 mmole ) of et 3 n via a syringe pump over a period of 12 hours . the reaction mixture was then extracted with h 2 o and saturated nahco 3 . drying over mgso 4 and removal of the solvent under reduced pressure gave the crude product . chromatography on silica gel , eluting with hexane / etoac ( 80 / 20 ) gave 5 . 18 g of the product ( isomer a ) as a white solid . the structure was confirmed by nmr and mass spectroscopy . continued elution from the column gave 3 . 16 g of isomer b as a white solid . the structure was confirmed by nmr and mass spectroscopy . ## str59 ## to a solution of 4 . 14 g ( 11 . 42 mmole ) of ## str60 ## was added 7 ml of 2 n naoh and the mixture stirred at room temperature for one hour . the reaction mixture was poured into water , cooled to 5 °, and acidified to ph 2 with 0 . 5 n hcl . the aqueous layer was extracted four times with ch 2 cl 2 and the combined organic layers dried over mgso 4 . removal of the solvent under reduced pressure gave 3 . 09 g of the product . the structure was confirmed by nmr and mass spectroscopy . ## str61 ## a solution of 2 . 5 g ( 7 . 48 mmole ) of ## str62 ## 0 . 83 g ( 8 . 22 mmole ) of et 3 n , 2 . 18 g ( 8 . 97 mmole ) of cad , and 1 . 21 g ( 8 . 97 mmole ) of hobt in 40 ml ch 2 cl 2 was cooled in ice and treated with 1 . 69 g ( 8 . 22 mmole ) of dcc . after stirring at 0 ° for one hour , the mixture was left at room temperature for two days . the solvent was removed under reduced pressure and the residue taken up in etoac and filtered . removal of the solvent gave the crude product . chromatography on silica gel , eluting with a gradient of 1 % to 1 . 5 % meoh in ch 2 cl 2 gave 4 . 29 g of the product . the structure was confirmed by nmr and mass spectroscopy .