Synthesis of D-(6R) - and D-(6S) -(6-2H1) glucose

Chemical synthesis ofD-(6R)- and D(6S)-(6-²H₁) glucose is described comprising (i) formation of 6-²H₁)-3-o-benzyl-5,6-dideoxy-l, 2-0-isopropylidene-α-D-xylo-hex-5-ynofuranose from D-glucose; (ii) stereospecific reduction of the deuterated acetylene functionality to (E)- or (Z)-deuterated olefin; (iii) stereospecific cis-dihydroxylation of the deuterated olefin; and (iv) separation of stereoisomers based on the intrinsic chirality of D-glucose and subsequent deprotection.     

A New Synthesis of (2S,3R,4R)-2-(Hydroxymethyl)pyrrolidine-3,4-diol

The title compound 6 was synthesized from 2,3,5-tri-O-benzyl-D -arabinofuranose ( 7 ) in three steps and 48% overall yield. Moreover, it was shown, in the case of γ-hydroxy amide 9 , that the Mitsunobu reaction is not suitable for the preparation of γ-lactams, because O-alkylation is predominant.     

Synthesis of 1-[6-Fluoro-(2S)-3H,4H-dihydro-2H-2-chromenyl]-(1R)-1,2- ethanediol and 1-[6-Fluoro-(2R)-3H,4H-dihydro-2H-2-chromenyl]- (1R)-1,2-ethanediol

Benzopyran compounds possess diverse pharmacological properties such as β-blockade, anticonvulsant and antimicrobial.[1,2] Our interest has been focused on the synthesis of 1-[6-Fluoro-2S]-3H,4H-dihydro-2H-2-chromenyl]-(1R)-1,2-ethanediol (6) and 1-[6-fluoro-(2R)-3H,4H-dihydro-2H-2-chromenyl]-(1R)-1,2-ethanediol (7) which are particularly convenient precursor to (S,R,R,R)-NE (8). 8 containing four asymmetrical carbon atoms was reported to be the most active isomer.[3] Chandrasekhar[4] has reported on the synthesis of 8. The key step to synthesize this compound is to obtain the chiral chromanone 6 and 7. 6 was accomplished in 8 steps by the Clasien rearrangement and a one-pot Sharpless asymmetric epoxidation, but the compound 7 was accomplished in 10 steps. Johannes[5] used Zr-catalytic kinetic resolution of allylic ethers and Mo-catalyzed chromene formation to synthesize 8 in 14 steps. However both of the methods request many synthetic steps and expensive reagents.     

Synthesis and modeling study of (2S,5R,6R)- and (2S,5R,6S)-6-hydroxy- 8-(1-decynyl)-benzolactam-V8 as protein kinase C modulators

[structures: see text] Both (2S,5R,6R)- and (2S,5R,6S)-6-hydroxy-8-(1-decynyl)benzolactam-V8 were designed and synthesized as PKC modulators. Biological assays reveal the (6R)-ligand to be 20-fold more potent than its (6S)-counterpart in binding to PKC alpha.     

Synthesis of (R)- and (S)-Oxymethylmorpholine Derivatives

(S)-N-benzyl-3-tert-butyldiphenylsilyloxymethylmorpholine and (R)-N-benzyl-3-benzyloxymethylmorpholine are synthesized starting from (R)-1-benzylglycerol.     

Heterotricyclodecane XX (+)-(1S, 3S, 6S, 8S)- und (−)-(1R, 3R, 6R, 8R)-2, 7-Dioxa-twista-4,9-dien

(+)-(1S, 3S, 6S, 8S)- and (?)-(1R, 3R, 6R, 8R)-2,7-dioxa-twista-4,9-diene. A synthesis and the determination of the sense of chirality of (+)-(1S, 3S, 6S, 8S)- and (?)-(1R, 3R, 6R, 8R)-2,7-dioxa-twista-4,9-diene ((+)- 5 and (?)- 5 , respectively) is described.     

Studies towards the synthesis of (1R,2S)- and (1S,2S)-1,2-epoxy-3-hydroxypropylphosphonates and (1S,2S)- and (1R,2S)-2,3-epoxy-1-hydroxypropylphosphonates

The trans-configured fosfomycin analogue, diethyl (1S,2S)-1,2-epoxy-3-hydroxypropylphosphonate, was synthesised by the intramolecular Williamson reaction of diethyl (1S,2R)-1,3-dihydroxy-2-mesyloxypropylphosphonate. The cis-analogue was obtained as O-ethyl or O,O-diethyl (1R,2S)-1,2-epoxy-3-hydroxypropylphosphonates, when (1R,2R)-1,3-dihydroxy-2-mesyloxypropylphosphonate or its 3-O-trityl derivative were used as starting materials, respectively. The intramolecular Williamson cyclisations of diethyl (1S,2R)- and (1R,2S)-1-benzyloxy-3-hydroxy-2-mesyloxypropylphosphonates led to diethyl (1S,2S)- and (1R,2S)-2,3-epoxy-1-benzyloxypropylphosphonates, respectively, with the concomitant formation of diethyl (E)-1-benzyloxy-3-hydroxyprop-1-en-1-phosphonate. From diethyl (1S,2S)- and (1R,2S)-2,3-epoxy-1-benzyloxypropylphosphonates, enantiomerically pure diethyl (1S,2S)- and (1R,2S)-1,2-dihydroxypropylphosphonates were obtained by catalytic hydrogenation, while diethyl (1S,2S)- and (1R,2S)-3-acetamido-1,2-dihydroxypropylphosphonates were produced after epoxide ring opening with dibenzylamine, acetylation and hydrogenolysis.     

Synthesis of (2S,3S)-[3-(2)H1]-4-methyleneglutamic acid and (2S,3R)-[2,3-(2)H2]-4-methyleneglutamic acid

(2S,3S)-[3-(2)H1]-4-Methyleneglutamic acid 1a and (2S,3R)-[2,3-(2)H2]-4-methyleneglutamic acid 1b have been synthesised for use in biosynthetic and metabolic studies.     

Biopreparation of (-)-(1S,3R,4S,6S)-6-hydroxymenthol and (-)-(1S,3R,4S)-1-hydroxymenthol from 1-menthol by Rhizoctonia solani AG-1-IA and IB

Microbial transformation of 1-menthol (1) by six isolates of soil-borne plant pathogenic fungi Rhizoctonia solani AG-1-IA (Rs24, Joichi-2 and RRG97-1) and AG-1-IB (TR22, R147 and 110.4) as a biocatalyst was investigated. Twenty one days precultivation of Rhizoctonia solani AG-1-IA Rs24 and AG-1-IB 110.4 showed excellent yield (98.5-98.6%) of (-)-(1S,3R,4S,6S)-6-hydroxymenthol (2) and (-)-(1S,3R,4S)-1-hydroxymenthol (3) from 1.     

(1S,6R)-1-羟基-6-(1,3-苯并二硫-2-氧)-3,5-环维生素D2的合成

以VD2为原料制备了1α，25－二羟基维生素D3的重要中间体（1S，6R）－1－羟基－6－（1，3－苯并二硫－2－氧）－3，5－环维生素D2。其中BDT（1，3－苯并二硫－2－氧）基团的引入有利于共轭三烯系统的保护。     

Synthesis of (5R)- and (5S)-5-Methyl-5, 6-dihydrouridine Derivatives

The hydrogenation of 2′, 3′-O-isopropylidene-5-methyluridine (1) in water over 5% Rh/Al₂O₃ gave (5 R)- and (5 S)-5-methyl-5, 6-dihydrouridine (2) , separated as 5′-O-(p-tolylsulfonyl)- (3) and 5′-O-benzoyl- (5) derivatives by preparative TLC. on silica gel and ether/hexane developments. The diastereoisomeric differentiation at the C(5) chiral centre depends upon the reaction media and the nature of the protecting group attached to the ribosyl moiety. The synthesis of iodo derivatives (5 R)- and (5 S)- 4 is also described. The diastereoisomers 4 were converted into (5 R)- and (5 S)-2′, 3′,-O-isopropylidene-5-methyl-2, 5′-anhydro-5, 6-dihydrouridine (7) .     

Enzymatic preparation of (1S,2R)- and (1R,2S)-stereoisomers of 2-halocycloalkanols

The stereoisomers of cis-2-halocycloalkanols were resolved by a kinetically controlled transesterification with vinyl acetate in the presence of lipases in organic media. High enantioselectivities (ee >98%) and good isolated yields were obtained for all substrates using the appropriate lipase. Burkholderia cepacia lipase was the most efficient enzyme for the resolution of these substrates. The enantiomeric purities of the compounds were defined by derivatization with Mosher’s acid and the absolute configurations were determined by chemical correlation.     

Asymmetric conjugate reductions with samarium diiodide: asymmetric synthesis of (2S,3R)- and (2S,3S)-[2-2H,3-2H]-leucine-(S)-phenylalanine dipeptides and (2S,3R)-[2-(2)H,3-2H]-phenylalanine methyl ester

The highly diastereoselective samarium diiodide and D(2)O-promoted conjugate reduction of homochiral (E)- and (Z)-benzylidene and isobutylidene diketopiperazines (E)-5,7 and (Z)-6,8 has been demonstrated. This methodology allows the asymmetric synthesis of methyl (2S,3R)-dideuteriophenylalanine 27 in > or = 95% de and >98% ee, and (2S,3R)- or (2S,3S)-dideuterioleucine-(S)-phenylalanine dipeptides 37 and 38 in moderate de, 66% and 74% respectively. A mechanism is proposed to account for this process.