Synthesis of new chiral amines with a cyclic 1,2-diacetal skeleton derived from (2R, 3R)-(+)-tartaric acid

The syntheses of new chiral cyclic 1,2-diacetals from (2R, 3R)-( )-tartaric acid are described. C(2)-symmetrical diamines were prepared via direct amidation of the tartrate or from the corresponding bismesylate via reaction with sodium azide. For C1-symmetrical compounds, the Appel reaction was used to form the key intermediate, a monochlorocarbinol, from the diol. Some of the new chiral compounds, produced in good to high yields, may be potentially useful as asymmetric organocatalysts or as nitrogen and sulfur chelating ligands for asymmetric metal catalyzed reactions. Thus, a bis-N-methyl-methanamine derivative, used in substoichiometric amounts, was found to catalyze the enantioselective addition of cyclohexanone to (E)-beta-nitrostyrene with high diastereoselectivity (syn / anti = 92:8), albeit giving moderate optical purity (syn: 30 %).     

(+)-Colletodiol : Synthesis from (S,S)-tartaric acid and (R)-3-hydroxy-butyric acid

E-(R)-5-Hydroxy-2-hexenoic acid (4) and the acetonide of E-(4R,5R,7R)-trihydroxy-2-octenoic acid (3) are joined to give, after deprotection, (+)-colletodiol (1). The syntheses of the two hydroxy-acids from poly-(R)-3-hydroxy-butanoate (PHB) and (?)-tartaric acid, respectively, are outlined.     

Chemoenzymatic synthesis of (R)-(+)-2-methylbutan-1-ol,a chiral synthon for the preparation of optically active pheromones

Optically active (R)-(+)-2-methylbutan-1-ol (which is not commercially available) was prepared by a chemoenzymatic synthesis, in which the key step involved a reduction catalyzed by baker's yeast. The synthon was used in the synthesis of (R)-10-methyldodecan-1-yl acetate, the chiral methyl-branched pheromone of Adoxophyes sp.     

Synthesis of a C(29)-C(51) subunit of spongistatin 1 (Altohyrtin A) starting from (R)-3-benzyloxy-2-methylpropan-1-ol

A protected C(29)-C(51) subunit ((+)-38) of spongistatin 1 has been obtained. Key steps involve the aldol condensation of (3S, 4R)-3-methyl-7-[(p-methoxybenzyl)oxy]-4-[(triethylsilyl)oxy]octan- 2-o ne ((-)-6) with (tert-butyl)dimethylsilyl 4-deoxy-2, 3-di-O-(methoxymethyl)-4-methyl-6-O-(tert-butyl)dimethylsilyl)-bet a-D -glycero-L-gluco-heptodialdo-1,5-pyranoside ((+)-7) and a C-glycosidation of (4R,7R&S,E)-7, 8-dichloro-2-methylidene-1-(trimethylsilyl)oct-5-en-4-yl p-methoxybenzoate (16). Aldehyde (+)-7 was derived from (R)-3-benzyloxy-2-methylpropan-1-ol ((+)-10) in 13 formal steps but requiring the isolation of five intermediate products only. The longest linear synthetic scheme converts (+)-10 into (+)-38 in 2% overall yield (isolation of 11 intermediate products).     

A useful chiral synthon from (R)-4-menthenone

Russian Chemical Bulletin -     

The acetate of (Z)-4-chloro-2-methyl-2-buten-1-ol. Stereoselective wittig synthesis of a new hemiterpenoid synthon

a synthetic method for the preparation of the acetate of (Z)-4-chloro-2-methyl-2-buten-1-ol, a precursor of the (Z)-hydroxy prenyl synthon is described. The use of such synthon in the preparation of a metabolite of a prenyl-containing substance is also illustrated.     

Enzymatic kinetic resolution of 1-(3′-furyl)-3-buten-1-ol and 2-(2′-furyl)-propan-1-ol

The enzymatic kinetic resolution of the racemic alcohols 1-(3′-furyl)-3-buten-1-ol (±)-1 and 2-(2′-furyl)propan-1-ol (±)-2 was investigated by screening a range of lipases and esterases for enantioselective transacylation, as well as for enantioselective hydrolysis. For both alcohols, lipase-catalyzed hydrolysis of the derived racemic acetate gave the best results for accessing the desired (S)-enantiomers. In the case of the secondary alcohol (±)-1, ASL turned out to be the optimum enzyme, whereas PPL was found to be superior in the case of the primary alcohol (±)-2. Additionally, an alternative access to (S)-2 via Oppolzer's camphor sultam methodology is described.     

(+)-(1S,2S,5R)-8-联苯薄荷醇的合成

以(R)-( )-pu legone为起始原料,经1,4-加成,还原两步反应合成了手性辅助试剂( )-(1S,2S,5R)-8-联苯薄荷醇及其差向异构体(-)-(1R,2S,5R)-8-联苯薄荷醇,总产率95%。其结构经1H NMR,13C NMR,IR,MS和X-射线衍射仪表征。     

合成(R)-2-异戊氧基丙醇的新方法

以(R)-1,2-丙二醇为原料,经伯醇羟基保护、仲醇O-异戊基取代、脱羟基保护三步反应合成了手性醇(R)-2-异戊氧基丙醇,其结构经NMR和MS确证.     

Synthesis of (4R)-Methylnonan-1-ol and (4R,8RS)-Dimethyldecanal from (S)-(+)-3,7-Dimethyl-1,6-octadiene

Optically active (4R,8RS)-dimethyldecanal, an analog of the aggregation pheromone of the flour beetles Tribolium confusum and T. Castaneum, and (4R)-methylnonan-1-ol, the sex pheromone of the yellow mealworm Tenebrio molitor L., are synthesized using ozonolytic transformation of (6R,10)-dimethyl-9-undecen-2-one to (6R)-methyl-9-hydroxynonan-2-one in the key step. The starting compound is available as enantiomerically enriched (ee ~50%) (S)-(+)-3,7-dimethyl-1,6-octadiene.     

Syntheses of (S)-(+)-trihexyphenidyl hydrochloride and (S)-(+)-procyclidine hydrochloride, two anticholinergics, using (S)-(-)-3-cyclohexyl-3-hydroxy-3-phenylpropanoic acid as chiral synthon

The absolute configuration of the more active (-)-enantiomer of the anticholinergic trihexyphenidyl hydrochloride has been established as (R) by syntheses of (S)-(+)-procyclidine hydrochloride, whose absolute configuration has been established previously, and (S)-(+)-trihexyphenidyl hydrochloride from the same chiral building block, viz. (S)-(-)-cyclohexyl-3-hydroxy-3-phenylpropanoic acid. Both enantiomers of this chiral synthon were prepared by optical resolution of the corresponding racemate, employing (R)- and (S)-1-phenylethylamine, respectively, as resolving agents.     

Efficient syntheses of four stable-isotope labeled (1R)-menthyl (1S,2S)-(+)-2-phenylcyclopropanecarboxylates

Many carbenoid cyclopropanation reactions promoted by chiral catalysts give product mixtures reflecting impressive diastereo- and enantioselectivities. Few provide a single chiral product efficiently. This limitation has been overcome in cyclopropanations of styrene and isotopically labeled styrenes with alpha-diazoacetates. Convenient syntheses on a 20 g scale of each of four chiral isotopically labeled (1R)-menthyl (1S,2S)-2-phenylcyclopropanecarboxylates (the 1-d-3-(13)C, 1,(3S)-d2, 1,2,(3S)-d3, and 1,3,3-d3 isotopomers) of better than 99% ee have been realized.     

Synthesis of (+)-1,3:2,5-dianhydroviburnitol ((+)-(1R,2R,3S,5R,6S)-4,7-dioxatricyclo[3.2.1.03,6]octan-2-ol)

Epoxidation of (?)-(1R,2R,4R)-2-endo-cyano-7-oxabicyclo[2.2.1]hept-5-en-2-exo-yl acetate ((?)-5) followed by saponification afforded (+)-(1R,4R,5R,6R)-5,6-exo-epoxy-7-oxabicyclo[2.2.1]heptan-2-one ((+)-7). Reduction of (+)-7 with diisobutylaluminium hydride (DIBAH) gave (+)-1,3:2,5-dianhydroviburnitol ( = (+)-(1R,2R,3S,4R,6S)-4,7-dioxatricyclo[3.2.1.0^3,6]octan-2-ol; (+)-3). Hydride reductions of (±)-7 were less exo-face selective than reductions of bicyclo[2.2.1]heptan-2-one and its derivatives with NaBH₄, AlH₃, and LiAlH₄ probably because of smaller steric hindrance to endo-face hydride attack when C(5) and C(6) of the bicyclo-[2.2.1]heptan-2-one are part of an exo oxirane ring.     

Synthesis of 1,2-dihydroxyindolizidines from 1-(2-pyridyl)-2-propen-1-ol

1-(2-Pyridyl)-2-propen-1-ol, obtained by vinylation of commercially available picolinaldehyde, resulted a good starting material for the synthesis of the indolizidine skeleton. In particular, a simple process involving bromination, reduction, and nucleophilic substitution (via elimination and addition) allowed an easy conversion of the starting material into (±)-lentiginosine in ~27% overall yield.