a plausible abiotic chemical route to 
 the canonical nucleotides 
 is a major goal in origins of life research .
recently , we 
 demonstrated the first chemical steps toward a divergent pyrimidine 
 and purine ribonucleotide synthesis .
a 
 one - pot multicomponent reaction was demonstrated to stereoselectively 
 tether and consequently regiospecifically glycosylate purine precursors 
 and masked pentose sugars , while concurrently furnishing known pyrimidine 
 precursors ( scheme 1 ) .
although rna has often been considered as a 
 candidate for the first 
 biopolymer of life , extant biology utilizes two chemically 
 distinct , but related , nucleotide polymers , rna and dna .
dna is usually 
 viewed as a late evolutionary adaptation of earlier rna - based life .
however , it would not be possible to make dna 
 without deoxyribonucleotides , and yet in the absence of dna there 
 is no obvious reason for the evolution of the biochemical pathways 
 for the synthesis of deoxyribonucleotides . only after the emergence 
 of dna as an important cellular component
would there have been a 
 strong selective pressure favoring the emergence of biochemical pathways 
 for the synthesis of deoxyribonucleotides from ribonucleotides . although 
 the advantages of dna as a medium for information storage are clear , 
 there has not until now been any reasonable hypothesis for how dna 
 could be 
invented by primitive cells in the absence 
 of pre - existing deoxyribonucleotides . in this paper
biochemically , 2-deoxyribonucleotides are synthesized by 
 chemo- and regio - specific reduction of ribonucleotides . in the absence of the complex and energetically costly 
 enzymatic resources required to regiospecifically deoxygenate ribonucleotides , 

abiological 2-deoxygenation of nucleotides requires site - specific ribo- or arabino - nucleoside deoxygenation . 
 in light of the difficulty of regioselective nucleotide deoxygenation 
 in the absence of sophisticated enzymatic control
, it would seem that 
 regiospecific positioning of a group / atom with the appropriate latent 
 potential reactivity could form the basis of an alternative pathway 
 to the 2-deoxyribonucleotides . in principle , a sufficiently 
 chemoselective reactivity difference could be exploited to generate 
 both ribonucleotides and 2-deoxyribonucleotides , simultaneously .
constitutional analysis of dna , 
 with respect to rna , in light of 
 the low dissociation energy of c 
s bonds , suggests that regiospecific positioning of sulfur at c2 
 could result in the chemical differentiation required for the divergent 
 synthesis of dna and rna monomers from common precursors ( scheme 2 ) .
oxazole 1a key ribonucleotide 
 precursor  is 
 derived from cyanamide 2 and glycolaldehyde 3 .
the c2-carbon atom of 
 aldehyde 3 is formally delivered to a ribonucleotide 
 as the c2 sugar carbon .
it is of note that aldehyde 3 is also the aldehyde precursor of serine 4 , 
 a proteinogenic amino acid , via strecker synthesis with ammonium cyanide 
 ( scheme 3 ) .
the 
 constitutional similarity of serine 4 and cysteine 5 , and their aldehyde precursors 3 and -mercapto - acetaldehyde 6 , suggests that both 3 and 6 must 
 be considered within our exploration of prebiotic azole synthesis .
specifically , we propose that the divergent reactivity 
 of glycolaldehyde 3 and -mercapto - acetaldehyde 6 with cyanamide 2 could lead , via 2-aminooxazole 1 and 2-aminothiazole 7 , to ribonucleotides and 2-deoxyribonucleotides , by desulfurization of c2 
 ( scheme 2 ) .
the importance of 2-aminothiazole 7 , and its derivatives , 
 has been recognized in medicinal chemistry , but though the synthesis of thiazole 7 in water has 
 been reported , the potential relevance 
 of thiazole 7 to the origins of life remains unexplored . 

the formation of oxazole 1 from cyanamide 2 and glycolaldehyde 3 at neutral ph requires stoichiometric 
 ( or excess ) cyanamide 2 and general acid 
aldehyde 6 , upon 
 imine formation with cyanamide 2 , has , like 3 , the potential to undergo 5-exo - dig cyclization 
 to furnish imine 14 ( or hemiaminal 15 ) as 
 shown in scheme 3 .
furthermore , we expected 
 the reaction to proceed more rapidly at neutral ph and be less prone 
 to stall at intermediates en route to thiazole 7 due 
 to the increased nucleophilicity of sulfur and greater aromaticity 
 of thiazoles with respect to oxazoles . to test this supposition , 
 -mercapto - acetaldehyde 6 ( 8.5 mm ) and 2 ( 15 , 26 , or 50 mm ) were incubated in 
 d2o at pd 7 and 20 c and a rapid ( ca
. 10 min ) quantitative 
 conversion of aldehyde 6 to hemiaminal 15 was observed ( see the supporting information 
 figure s1 ) .
over the course of several hours , 15 dehydrated to furnish thiazole 7 ( see supporting information figures s2 and s3 ) .
it is of note that excess aldehyde 6 did not 
 lead to further reaction of thiazole 7 .
moreover , at 
 elevated concentration ( > 150 mm ) 2-aminothiazole 7 was 
 observed to directly crystallize from water , and a crystal structure 
 of thiazole 7 is shown in scheme 3 .
next we investigated the concomitant synthesis 
 of oxazole 1 and thiazole 7 . in the presence 
 of excess cyanamide 2
( 2.25 equiv ) , rapid and 
 stoichiometric conversion of glycolaldehyde 3 ( 1 equiv ) 
 and -mercapto - acetaldehyde 6 ( 1 equiv ) to hemiaminals 11 and 15 , respectively , was observed in water . 
 at high ph / pd ( ph / pd
> 9 ) specific base catalysis or in 1 m phosphate 
 solution ( ph / pd 6.57.5 ) general acid  base catalysis 
 furnish oxazole 1 and thiazole 7 over the 
 course of 2436 h at ambient temperature ( scheme 3 ; see supporting information figure 
 s8s10 ) . at neutral pd , selective 
 dehydration of 15 to liberate thiazole 7 was observed .
limiting cyanamide 2 ( 2/3/6  0.8:1:1 ) also resulted in the specific 
 generation of thiazole 7 , even in 1 m phosphate solution 
 ( ph 7 ; see supporting information figure 
 s9 ) .
it is likely that the rapid 5-exo - dig cyclization 
 of imine 12/ hemiaminal 13 leads to the 
 selective sequestration of cyanamide 2 in thiazole 7 .
we did not observe significant homo- and hetero - aldol 
 reaction 
 during the reaction of glycolaldehyde 3 and mercaptoacetaldehyde 6 with either excess or limiting cyanamide 2 between 
 ambient temperature and 60 c in 1 m phosphate solution at ph 
 7 .
interestingly , we also found that , like oxazole 1 , 
 thiazole 7 is easily sublimed ( see supporting information figure s4 ) , suggesting possible geochemical 
 routes to the distribution , separation , and purification of thiazole 7 under abiotically plausible conditions . sublimation from 
 a mixture of oxazole 1 and thiazole 7 resulted 
 in the isolation of both azoles as colorless crystalline solids .
partial 
 sublimation of a mixture of oxazole 1 and thiazole 7 ( 1:1 ) resulted in the isolation 4:12:1 oxazole 1/thiazole 7 , at 50 c between 1 and 24 
 h at ambient pressure , indicating the more rapid but comparable sublimation 
 rate of oxazole 1 relative to thiazole 7 .
complete sublimation was observed after 2 d at 60 c to afford 
 1:1 mixture of crystalline azoles at ambient pressure .
we then examined the multicomponent reaction of thiazole 7 , 4-amino - imidazole 5-carboxamide 16 , and a series of aldehydes .
equimolar quantities of thiazole 7 and aliphatic aldehydes 
 ( including formaldehyde , acetaldehyde , propionaldehyde , and cyclobutaldehyde ) 
 with excess amino - imidazole 16 ( 1.23 equiv ) furnished 
 high yields ( 7590% ) of thiazolines 17 , 18 , 19 , and 20 , respectively , at 
 ph 5 .
the multicomponent reactions were found to be robust at multi - gram 
 scale and comparable diastereoselectivity was observed in the reaction 
 of aliphatic aldehydes with oxazole 1 or thiazole 7 and amino - imidazole 16 ( via imine 21 r = alkyl ; d.r.= 2.5:14:1 threo / erythro ) .
compounds 17 , threo-18 and erythro-18 , and the major isomers of 19 and 20 were isolated by fractional crystallization , and the crystal 
 structures are shown in scheme 4 . to continue our investigation into the potential 
 of multicomponent 
 assembly of nucleotides we studied the participation of thiazole 7 in carbon 
carbon bond - forming reaction with -hydroxyaldehydes 
 and imines derived from -hydroxyaldehydes in water .
incubation of equimolar aldehyde 3 , 2-aminothiazole 7 , and amino - imidazole 16 for 5 d in water at ph 46 at 20 c gave a high yield 
 of c4-thiazoline 23 ( 80% isolated yield ) as 
 1.2:1 erythro / threo mixture of diastereomeric 
 products .
surprisingly , this signified that the facial selectivity 
 of thiazole 7 is significantly relaxed with respect to 
 oxazole 1 and imine 21 ( r = ch2oh ) .
however , both erythro-23 and threo-23 were formed with complete annulation 
 control ( > 99% , see h nmr spectrum shown in supporting information figure s28 ; single crystal 
 x - ray structures of erythro-23 and threo-23 are shown in scheme 5 ) . upon investigation of 
 the parallel mcr with the c3-synthon 
 glyceraldehyde 22 , comparable efficiency in the synthesis 
 of c5-thiazoline 24 ( 70% isolated yield ) was 
 observed .
again , exclusive 6-exo - trig annulation 
 is observed ; however , in this case , 24 is furnished with 
 significant diastereoselectivity ( d.r.= 9:5:1.1:1 , see scheme 5 and supporting information figure s35 ) .
isolation of the two major isomers , crystallization , 
 and x - ray diffraction proved their xylo- and lyxo - configuration .
the diastereoselectivity 
 obtained , upon carbon  carbon bond formation is proposed to 
 result from intramolecular hydrogen - bonding and concomitant steric 
 impedance of thiazole addition to the si - face of 
 imine 21 ( see supporting information scheme s1 ) . although the facial selectivity 
 of the nucleophile 7 has been relaxed with respect to 
 the comparable reaction of 1 , the facial 
 selectivity of the glyceraldehyde - imine 21 ( r = ch2oh ) is retained .
this is important 
 with respect to purine nucleotide synthesis by 3-purine tethering , 
 which necessarily requires n3-displacement and c3-inversion . 

furthermore , as well as regiospecific tethering of 16 and consequent delivery of n1 to the anomeric carbon atom , reaction 
 of thiazole 7 with imine 21 regiospecifically 
 delivers sulfur to c2 , which is of significant interest with 
 regards to the potential synthesis of 2-deoxynucleotides by 
 c2-desulfurization .
the multicomponent tricyclic thiazoline products 1724 were uncontaminated with homoaldolization 
 and homo - mannich byproducts .
additionally , oxazole 1 is 
 known to react efficiently with -hydroxyaldehydes in a ph - dependent 
 bimolecular domino - reaction . in striking 
 contrast ,
carbon bond formation was observed 
 by h nmr analysis upon incubation of thiazole 7 with either glycolaldehyde 3 or rac - glyceraldehdye 22 in d2o ( pd 39 , 
 4100 c ) . instead , over a period of 4 days at pd 7 ,
crystal 
 formation was observed from an aqueous solution containing 3 ( 100 mm ) and thiazole 7 ( 100 mm ) at 20 c .
single crystal x - ray diffraction of a crystal 
 isolated directly from the reaction supernatant proved that the structure 
 was aminal 25 ( scheme 6 ) .
though nmr studies confirmed that rac-22 formed hemiaminal 26 and 
 aminal 27 with 
 thiazole 7 in d2o , no aminal crystallization 
 was observed in solutions of rac-22 and 7 , even at significantly elevated concentrations ( 500 mm to 
 2 m ) or with substoichiometric quantities of rac-22 . to test whether the change in solubility properties was 
 due to the increased number of hydroxyl moieties or perhaps due to 
 the differential solubility and packing properties of rac-27 with respect to the achiral aminal 25 , we investigated the solubility properties of the aminal structures 
 formed in a mixture of d - glyceraldehyde 22 and 
 thiazole 7 .
intriguingly , we found that at 100 mm concentration , d-27 now crystallized from water at 20 c . 

nmr analysis showed a 1:2 ratio of 22/7 and 
 recrystallization ( 10:1 h2o / etoh ) allowed for crystallographic 
 confirmation of the aminal structure ( scheme 6 ) .
in summary , our results suggest that in a sulfur - rich 
 prebiotic 
 environment , oxazole 1 and thiazole 7 could 
 be formed together under the same conditions , as long as both glycolaldehyde 3 and its thiol analogue , -mercapto - acetaldehyde 6 , were present along with cyanamide 2 . in such 
 mixed reactions ,
the absence of any interference 
 between oxazole and thiazole synthesis shows that these potential 
 precursors of deoxynucleotides and ribonucleotides could indeed be 
 formed at the same time in the same conditions .
we have also found 
 that two abiotically plausible methods for the purification of oxazole 1 , namely , crystallization and sublimation , also apply to 
 thiazole 7 .
however , the chemical reactivities of oxazole 1 and thiazole 7 are quite different , suggesting 
 that the subsequent pathways would diverge .
the most striking 
 difference between the reactivity of oxazole 1 and thiazole 7 is the failure of the thiazole 
 to react with aldehydes to form the thiazoline precursors of the ( thio)pyrimidine 
 nucleotides .
the most likely explanation for this difference is the 
 increased aromaticity of the thiazole relative to the oxazole , and 
 thus decreased nucleophilicity of c5 .
we are currently investigating 
 an alternative synthesis of 2-deoxyribo - pyrimidine nucleotides 
 mediated by c2-inversion of anhydronucleotide 28 ( scheme 1 ) .
however , during 
 the course of efforts to observe two - component reactivity of thiazole 7 with aldehydes , we observed instead the crystallization 
 of glycolaldehyde 3 and homochiral ( but not racemic ) 
 glyceraldehyde 22 ( two known ribonucleotide precursors ) as aminals directly from water .
the facile reversibility of aminal 
 formation suggests that the chemical sequestration and protection 
 of c2- and c3-aldehyde nucleotide synthons by 
 another important class of nucleotide synthon ( azoles ) may have provided 
 a route to the concentration , purification , and stabilization of the 
 necessary aldehyde precursors of nucleotides .
although these aldehydes 
 can in principle be readily synthesized by a variety of routes , their high reactivity has until now made it difficult to conceive 
 of means for accumulating large reservoirs of these essential starting 
 materials in a prebiotic context . by exploring the multicomponent 
 reactivity of thiazole 7 , together with aldehydes and 
 the purine precursor amino - imidazole 16 , we have demonstrated 
 a selective and high yielding 3-component 
 carbon  carbon bond - forming reaction that chemospecifically 
 furnishes masked-2-thiosugars regiospecifically tethered to 
 an amino - imidazole purine - precursor .
the facial selectivity of thiazole 7 , upon addition to -hydroxyaldehyde - imines , is quite 
 relaxed ( relative to oxazole 1 ) , resulting in low diastereoselectivity 
 at c2 ; however , this is inconsequential with regards to the 
 proposed deoxynucleotide synthesis because c2 would be rendered 
 achiral following desulfurization .
in contrast , we observed very high 
 diastereoselectivity of nucleophilic addition of thiazole 7 to imine 21 , generating almost exclusively the lyxo and xylo isomers with controlled n9c1 
 annulation .
the conversion of the resulting c5-thiazolines 
 to 2-deoxyribo - purine nucleotides requires three additional 
 steps : c3-inversion to release the purine - precursor from its 
 tethered attachment to c3 , completion of the purine heterocycle , 
 and chemospecific desulfurization of c2. these steps are currently under investigation in our laboratories 
 as part of our continuing studies aimed at the abiotic synthesis of 
 2-deoxyribonucleotides .
finally , it is of note that if life emerged in an environment containing 
 both ribo- and 2-deoxyribonucleotides , it is likely that the 
 first biopolymers were heterogeneous in composition , that is , composed 
 of a mixture of ribo- and deoxyribonucleotides , and perhaps other 
 compatible nucleotides .
recent work has shown that functional biopolymers , 
 in the form of aptamers with highly specific molecular recognition 
 properties , can be derived by in vitro evolution from libraries of 
 polynucleotides composed of randomly interspersed ribo- and deoxyribo - nucleotides . thus , chimeric rna / dna polymers may have been 
 sufficient for the emergence of life .
the primordial biochemical exploitation 
 of a mixed rna and dna genetic system could eliminate the requirement 
 for a genetic takeover ( of rna by dna ) , and would arguably result 
 in a simplification of the transition from chemistry to biology
. however , 
 such mixed - composition polymers have neither the advantageous stability 
 of dna , nor the optimal functional characteristics of rna .
thus , rna 
 and dna may have emerged as early and contemporaneous specializations 
 of a primitive mixed biopolymer .
reagents and solvents were purchased 
 from sigma - aldrich , tci america , frontier scientific , or cambridge 
 isotope laboratories .
flash column chromatography was carried out 
 on merck 9385 silica gel 60 ( 230400 mesh ) .
nmr spectroscopy 
 was carried out on a varian nmr spectrometer ( oxford as-400 ) or a 
 bruker nmr spectrometer ( avanceiii 600 ) operating at 25 c probe 
 temperature ( unless otherwise specified ) .
when possible , the chemical 
 shift of the corresponding solvent was used as a reference .
chemical 
 shift values are reported in parts per million ( ppm ) and j - couplings are recorded in hertz ( hz ) .
electrospray mass spectrometry 
 was recorded on a bruker daltonics esquire 6000 esi - ms .
high resolution 
 mass spectrometry was carried out on a waters q - tof micro lc / ms / ms 
 system .
infrared spectra were recorded as manually pressed kbr discs 
 on a perkinelmer spectrum 100 series ft - ir spectrometer .
single crystal 
 x - ray crystallography was carried out with a bruker apex ii ccd diffractometer 
 ( mo k radiation ,  = 0.71073  ) , equipped with an 
 oxford cryosystems nitrogen flow apparatus , at 100 k. data integration 
 down to 0.76  resolution was carried out using saint v7.46 a 
 ( bruker diffractometer , 2009 ) with reflection spot size optimization . 

absorption corrections were made with the program sadabs ( bruker diffractometer , 
 2009 ) .
the structure was solved by the direct methods procedure and 
 refined by least - squares methods against f by using shelxs-97 and shelxl-97 ( sheldrick , 2008 ) .
mercaptoacetaldehyde 6 and cyanamide 2 ( 0.51.5 equiv ) were 
 dissolved in h2o , d2o or phosphate buffer ( 1 
 ml ) at ph / pd 7.0 .
reaction progress was monitored by the h nmr spectroscopy ( see the supporting information , figure s1 ) .
an initial concentration of 100 mm led to direct crystallization 
 of 7 ( 60% isolated yield of crystals ) .
alternatively , 
 upon complete conversion ( by nmr spectroscopy ) , the solution was concentrated 
 and 7 recovered by sublimation .
compound 7 ( 15 g ) was placed in a covered beaker or erlenmeyer flask 
 and warmed from beneath to 40 c .
sublimate was collected on 
 flask / beaker sides and cover at ambient temperature ( see figure s4 ) or on a water - cooled coldfinger ( 5 
 c ) .
ir ( solid , cm ) : 3407 , 3285 , 3120 , 3086 , 1622 , 1518 , 1488 .
h nmr ( 400 mhz ; dmso ) : h 6.90 ( d , j = 3.7 , 1h , h(c4 ) ) , 6.84 ( s , 2h , nh2 ) , 6.51 ( d , j = 3.7 , 1h , h(c5 ) ) .
c nmr ( 101 mhz ; dmso ) : c 169.5 , 139.3 , 107.1 .
ms 
 esi ( pos . ) 101 ( 100% , [ m + h ] ) .
glycolaldehyde 3 ( 1 equiv ) , 
 mercaptoacetaldehyde 6 ( 1 equiv ) , and cyanamide 2 ( 0.55 equiv ) were dissolved in h2o / d2o ( 1 ml ) at ph / pd 7 , 10 or 12 , or 1 m phosphate buffer ( 1 
 ml ) at ph / pd 6.57.0 .
reaction progress was monitored by the h nmr spectroscopy ( see the supporting 
 information , figure s810 ) . an initial concentration 
 of 200 mm of 2 , 3 and 6 led 
 to direct crystallization of 15 ( 510% isolated 
 yield of crystals ) .
alternatively , upon complete conversion ( by nmr 
 spectroscopy ) , the solution was concentrated and 7 and 1 were recovered by sublimation .
compounds 7 and 1 ( 1:1 ; 100 mg ) as fine powder or film ( evaporated water ) 
 were deposited in a covered glass tube ( 10 cm  1 cm ) .
a temperature 
 gradient ( 40 , 50 , or 60 c to ambient temperature ) was set up 
 across the tube and a mixture of crystalline thiazole 7 and oxazole 1 were isolated at ambient temperature 
 as a deposit upon the glass wall of the tube .
aldehyde ( 0.491.0 equiv ) was added to a solution of 7 in h2o at ph 7  0.2 .
the solution was then 
 incubated at room temperature for 510 d ; the resultant solid 
 was then isolated by filtration or trituration and washed twice with 
 ethanol and once with ice cold water .
d - glyceraldehyde 22/thiazole 7 crystals were then recrystallized 
 from aqueous ethanol ( 10:1 h2o / etoh ) .
ir ( solid , cm ) : 3213 ( br ) , 2966 , 2934 , 2869 , 
 1589 , 1539 , 1497 .
ir ( solid , cm ) : 3326 ( br ) , 3244 , 3113 , 2948 , 
 2933 , 2901 , 2882 , 1536 , 1489 .
aldehyde 
 ( 50250 mm , 1 equiv ) was added to a solution of 7 ( 1.1 equiv ) and 5-aminoimidazole-4-carboxamide 16 ( 1.53.0 
 equiv ) in h2o at ph 5.0  0.2 .
the reaction was stirred 
 under an argon atmosphere until no residual aldehyde was detectable 
 following lyophilization and analysis by h nmr .
the reaction 
 was lyophilized and purified by silica gel column chromatography ( ch2cl2/meoh , 10:0 to 6:4 ) .
the major product(s ) were 
 concentrated and recrystallized from ethanol / water or dichloromethane / methanol 
 mixtures .
ir ( solid , cm ) : 3333 , 3179 , 2977 , 2922 , 2860 , 1636 , 1607 , 1580 , 
 1558 .
h nmr ( 400 mhz ; d2o ) : h 7.22 ( s , 1h , ar ) , 5.85 ( d , j = 6.0 , 1h , h(c1 ) ) , 
 4.18 ( ddd , j = 7.8 , 6.0 , 4.1 , 1h , h(c2 ) ) , 
 3.39 ( abx , j = 12.8 , 4.1 , 1h , h(c3 ) ) , 
 3.20 ( abx , j = 7.8 , 1h , h(c3 ) ) .
h nmr ( 400 mhz ; dmso ) : h 7.26 ( d , j = 1.1 , 1h , ar ) , 5.91 ( d , j = 6.1 , 1h , 
 h(c1 ) ) , 4.294.25 ( ddd , j = 
 7.0 , 6.1 , 3.8 , 1h , h(c2 ) ) , 3.41 ( abx , j = 13.0 , 3.8 , 1h , h(c3 ) ) , 3.18 ( abx , j = 13.0 , 7.0 , 1h , h(c3 ) ) .
c nmr ( 101 
 mhz ; dmso ) : c 166.6 , 161.4 , 141.6 , 129.4 , 111.4 , 
 79.5 , 48.0 , 42.2 .
cambridge 
 crystallographic data centre deposition number 864226 . 18 : yield > 85% d.r.= 2.5:1 erythro-18 ( minor ) : rf = 0.25 ( ch2cl2/meoh 7:3 ) .
ir ( solid , cm ) : 3437 , 3387 , 3292 , 3123 , 2975 , 2856 , 1638 , 1613 , 1571 .
h nmr ( 400 mhz ; dmso ) : h 7.05 ( s , 1h , ar ) , 6.97 
 ( s , 2h , nh2 ) , 6.68 ( br d , j = 19.9 , 2h , 
 nh2 ) , 5.95 ( d , j = 6.4 , 1h , h(c1 ) ) , 
 5.89 ( s , 1h , hn ) , 4.54 ( ddd , j = 6.4 , 2.5 , 1.7 , 1h , 
 h(c2 ) ) , 3.78 ( qd , j = 6.4 , 2.6 , 1h , 
 h(c3 ) ) , 1.25 ( d , j = 6.4 , 3h , h(c4 ) ) .
c nmr ( 101 mhz ; dmso ) : c 166.7 , 165.2 , 
 141.4 , 128.4 , 111.6 , 79.4 , 58.6 , 46.7 , 22.7 .
hrms esi [ m + na ] calc . for c9h12n6osna 275.0691 ; 
 obs .
ir ( solid , 
 cm ) : 3391 , 3302 , 3103 , 2972 , 2865 , 1651 , 1621 , 
 1582 . h 
nmr ( 400 mhz ; dmso ) : h 7.33 ( s , 1h ) , 6.96 ( s , 1h ) , 6.76 ( d , j = 27.2 , 
 1h ) , 6.20 ( s , 1h ) , 6.00 ( d , j = 6.1 , 1h ) , 3.85 ( dd , j = 9.5 , 6.3 , 1h ) , 3.243.17 ( m , 1h ) , 1.31 ( d , j = 6.2 , 1h ) .
c nmr ( 101 mhz ; dmso ) : c 166.7 , 159.2 , 141.3 , 129.7 , 111.3 , 79.1 , 54.6 , 48.9 , 20.4 . 

hrms esi [ m + na ] calc . for c9h12n6osna 275.0691 ; obs . 275.0686 .
19 : yield 
 > 85% d.r.= 3:1 rf = 0.25 ( ch2cl2/meoh 7:3 ) .
threo-19 ( major ) : 
 ir ( solid , cm ) : 3432 , 
 3371 , 3314 , 3105 , 2966 , 2930 , 1645 , 1604 , 1575 .
h nmr 
 ( 400 mhz ; dmso ) : h 7.04 ( s , 1h , ar ) , 6.97 ( s , 2h , 
 nh2 ) , 6.67 ( br.s , 2h , nh2 ) , 5.95 ( d , j = 6.4 , 1h , h(c1 ) ) , 5.85 ( s , 1h , nh ) , 4.60 
 ( d , j = 6.3 , 1h , h(c2 ) ) , 3.60 ( t , j = 6.9 , 1h , h(c3 ) ) , 1.741.63 ( m , 
 1h , h(c4h ) ) , 1.461.35 ( m , 1h , h(c4h ) ) , 
 0.94 ( t , j = 7.3 , 3h , me ) .
c nmr ( 101 
 mhz ; dmso ) : c 166.8 , 165.3 , 141.3 , 128.3 , 111.6 , 
 79.6 , 56.5 , 52.5 , 29.8 , 10.6 .
hrms esi [ m + na ] calc . 
 for c10h14n6osna 289.0848 ; obs .
threo-20 ( major ) : ir ( solid , cm ) : 3404 , 
 3109 , 2923 , 2525 , 2293 , 1605 , 1581 , 1548 , 1512 .
h nmr 
 ( 400 mhz ; dmso ) : h 6.70 ( s , 1h , ar ) , 5.58 ( d , j = 6.4 , 1h , h(c1 ) ) , 4.28 ( dd , j = 6.3 , 2.1 , 1h , nh ) ) , 2.57 ( dd , j = 9.0 , 2.2 , 1h , 
 h(c2 ) ) , 0.39 ( qt , j = 8.1 , 4.2 , 1h , 
 h(c3 ) ) , 0.18 ( quintet , j = 8.7 , 2h , 
 h2(c4 ) ) , 0.00 ( d , j = 
 3.9 , 2h , h2(c4 ) ) .
c nmr ( 101 
 mhz ; dmso ) : c 164.4 , 163.1 , 138.8 , 126.1 , 109.2 , 
 77.2 , 54.9 , 53.6 , 15.1 , 2.0 , 0.0 hrms esi [ m+na ] calc . 
 for c11h14n6osna 301.0846 ; obs .
ir ( solid , cm ) : 3363 , 3213 , 3192 , 2920 , 2844 , 2375 , 1626 , 1592 , 1547 , 1519 .
h nmr ( 400 mhz ; d2o ) : h 7.23 
 ( s , 1h , ar ) , 5.81 ( d , j = 7.5 , 1h , h(c1 ) ) , 
 4.99 ( dd , j = 7.5 , 2.5 , 1h , h(c2 ) ) , 
 3.75 ( ddd , j = 2.5 , 5.9 , 5.2 1h , h(c3 ) ) , 
 3.53 ( abx , j = 12.5 , 5.2 , 1h , h(c4 ) ) , 
 3.49 ( abx , j = 12.1 , 5.9 , 1h , h(c4 ) ) .
h nmr ( 400 mhz ; dmso - d6 ) : h 7.05 ( s , 1h , ar ) , 6.97 ( s , 2h , conh2 ) , 6.66 ( bs , 
 2h , nh2 ) , 6.05 ( s , 1h , nh ) , 6.02 ( d , j = 6.3 , 1h , h(c1 ) ) , 5.29 ( t , j = 
 0.5 , 1h , oh ) , 4.48 ( d , j = 5.9 , 1h , h(c2 ) ) , 
 3.78 ( m , 1h , h(c3 ) ) , 3.60 ( m , 1h , h(c4 ) ) , 
 3.27 ( m , 1h , h(c4 ) partially obscured by dmso residual 
 solvent signal ) .
c nmr ( 101 mhz ; dmso ) : c 166.8 , 165.9 , 141.2 , 128.3 , 111.8 , 80.2 , 65.3 , 53.6 , 53.0 . hrms 
 esi [ m + na ] calc . for c9h12n6o2sna 291.0640 ; obs . 291.0640 .
ir ( solid , 
 cm ) : 3330 , 3212 , 3111 , 2950 , 2926 , 2853 , 2394 , 
 1631 , 1568 .
h nmr ( 400 mhz ; d2o ) : h 7.35 ( s , 1h , ar ) , 5.98 ( d , j = 5.9 , 1h , 
 h(c1 ) ) , 4.09 ( dd , j = 7.9 , 6.5 , 1h , 
 h(c2 ) ) , 3.80 ( abx , j = 12.0 , 2.4 , 
 1h , h(c4 ) ) , 3.62 ( abx , j = 11.9 , 
 5.7 , 1h , h(c4 ) ) , 3.453.41 ( m , 1h , h(c3 ) ) .
h nmr ( 400 mhz ; dmso ) : h 7.31 ( s , 1h , ar ) , 
 6.99 ( s , 2h , nh2 ) , 6.76 ( bd , j = 10.1 , 
 2h , c(o)nh2 ) , 6.35 ( s , 1h , nh ) , 6.02 ( d , j = 6.2 , 1h , h(c1 ) ) , 5.21 ( dd , j = 
 6.5 , 4.6 , 1h , ho ) , 3.95 ( dd , j = 9.7 , 6.2 , 1h , h(c2 ) ) , 
 3.73 ( dt , j = 11.1 , 3.8 , 1h , h(c4 ) ) , 
 3.463.41 ( m , inc .
j = 11.1 , 1h , h(c4 ) 
 partially obscured by h2o signal ) , 3.18 ( m , inc .
c nmr 
 ( 101 mhz ; dmso ) : c 166.5 , 159.2 , 140.9 , 129.3 , 111.0 , 
 79.0 , 63.2 , 54.4 , 49.0 .
ir ( solid , cm ) : 3344 , 3106 , 2917 , 
 2833 , 1627 , 1553 .
h nmr ( 400 mhz ; dmso ) : h 7.14 ( s , 1h , ar ) , 6.90 ( s , 2h , nh2 ) , 6.59 ( bs , 1h , nh2 ) , 6.35 ( s , 1h , nh ) , 5.93 ( d , j = 6.1 , 1h , 
 h(c1 ) ) , 4.98 ( d , j = 6.1 , 1h , ho ) , 
 4.93 ( t , j = 5.4 , 1h , ho ) , 4.19 ( dd , j = 7.6 , 6.2 , 1h , h(c2 ) ) , 3.593.54 ( m , 1h , 
 h(c4 ) ) , 3.49 ( abx , j = 10.9 , 5.0 , 
 1h , h(c5 ) ) , 3.463.41 ( m , inc .
j = 10.9 , 1h , h(c5 ) ) , 3.363.34 ( m , inc . j = 7.6 hz , 1h , h(c3 ) ) .
c nmr 
 ( 100 mhz ; dmso ) : c 166.6 , 160.5 , 148.7 , 141.2 , 128.6 , 
 110.8 , 78.38 , 78.35 , 71.2 , 63.2 , 53.3 , 50.5 .
ir ( solid , cm ) : 3309 , 3125 , 
 2936 , 2835 , 1632 , 1565 .
h nmr ( 400 mhz ; d2o ) : 
 h 7.26 ( s , 1h , 

ar ) , 5.94 ( d , j = 5.8 , 1h , h(c1 ) ) , 
 4.21 ( t , j = 6.7 , 1h , h(c2 ) ) , 3.73 
 ( m , 1h , h(c4 ) ) , 3.69 ( abx , j = 11.8 , 
 4.5 , 1h , h(c5 ) ) , 3.64 ( abx , j = 11.8 , 
 4.5 , 1h , h(c5 ) ) , 3.52 ( dd , j = 7.5 , 
 1.9 , 1h , h(c3 ) ) .
h nmr ( 400 mhz ; dmso ) : 
 h 7.05 ( s , 1h , ar ) , 6.99 ( s , 1h , nh2 ) , 
 6.67 ( bs , 1h , nh2 ) , 6.18 ( s , 1h , nh ) , 6.01 ( d , j = 6.3 , 1h , h(c1 ) ) , 5.44 ( d , j = 6.0 , 1h , ho ) , 4.85 ( t , j = 5.5 , 1h , ho ) , 4.55 
 ( d , j = 6.1 , 1h , h(c2 ) ) , 3.69 ( d , j = 8.3 , 1h , h(c4 ) ) , 3.54 ( abx(oh ) , j = 11.3 , 5.5 , 1h , h(c5 ) ) , 3.47 ( abx(oh ) , j = 11.3 , 5.5 , 1h , h(c5 ) ) , 3.20 ( m , 1h , 
 h(c3 ) ) .
c nmr ( 101 mhz ; dmso ) : c 166.5 , 165.9 , 141.0 , 127.9 , 111.5 , 100.0 , 79.7 , 75.1 , 63.5 , 
 53.5 . hrms esi [ m + na ] calc . for c10h14n6o3sna 321.0746 ; obs . 321.0750 .
 we propose a novel pathway for the prebiotic synthesis 
 of 2-deoxynucleotides . 
 
 consideration of the constitutional chemical relationships between 
 glycolaldehyde and -mercapto - acetaldehyde , and the corresponding 
 proteinogenic amino acids , serine and cysteine , led us to explore 
 the consequences of the corresponding sulfur substitution for our 
 previously proposed pathways leading to the canonical ribonucleotides . 
 
 we demonstrate that just as 2-aminooxazole  an important prebiotic 
 ribonucleotide precursor  is readily formed from glycolaldehyde 
 and cyanamide , so is 2-aminothiazole formed from -mercapto - acetaldehyde 
 and cyanamide in water at neutral ph . 
 indeed , both the oxazole and 
 the thiazole can be formed together in a one - pot reaction , and can 
 be co - purified by crystallization or sublimation . 
 we then show that 
 2-aminothiazole can take part in a 3-component carbon  
 carbon 
 bond - forming reaction in water that leads to the diastereoselective 
 synthesis of masked 2-thiosugars regiospecifically tethered 
 to purine precursors , which would lead to 2-deoxynucleotides 
 upon desulfurization . 
 the possibility of an abiotic route to the 2-deoxynucleotides 
 provides a new perspective on the evolutionary origins of dna . 
 we 
 also show that 2-aminothiazole is able to sequester , through reversible 
 aminal formation , the important nucleotide precursors glycolaldehyde 
 and glyceraldehyde in a stable , crystalline form . 
Introduction
Results and Discussion
Summary
Experimental Section