Methyl (3R,5R)-3,5-dihydroxydecanoate in the asymmetric synthesis of Idea Leuconoe pheromone and formal syntheses of (+)-(3R,5R)-3-hydroxydecano-5-lactone, verbalactone, and Tolypothrix pentaether

A simple and efficient asymmetric synthesis of (5S,7R)-7-hydroxydodecano-5-lactone, a component of the giant danaine butterfly Idea leuconoe pheromone, and formal syntheses of (+)-(3R,5R)-3-hydroxydecano-5-lactone, verbalactone, and Tolypothrix pentaether have been accomplished starting from methyl (3R,5R)-3,5-dihydroxydecanoate. The latter is obtained from methyl 3-[(tributylstannyl)methyl]but-3-enoate using Keck allylation in the key step of the construction of its carbon skeleton.     

Synthesis of (+)-(3R,5R)-3-Hydroxy-5-decanolide and Massoialactone,and Formal Synthesis of Verbalactone

Total synthesis of (3R, 5R)-(+)-3-hydroxy-5-decanolide (1) and massoialactone (2), and formal synthesis of verbalactone (3), have been reported.     

A Stereoselective Total Synthesis of Verbalactone

A stereoselective total synthesis of verbalactone has been achieved starting from commercially available hexanal. The sequence involves Maruoka allylation, diastereoselective iodine‐induced electrophillic cyclization, ring opening of epoxide, and Yamaguchi macrolactonization as the key steps.     

Stereoselective synthesis of 3-mono- and 1,3-disubstituted 4-phenyl-1,2,3,4-tetrahydroisoquinolines

(1S,2S)-(+)-Thiomicamine was transformed in high yield and with high diastereoselectivity into (3R,4R)-4-phenyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid and enantiomerically pure (3R,4R)-3-hydroxymethyl-4-phenyl- and (1R,3R,4R)-3-hydroxymethyl-1-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline derivatives.     

Chemoenzymatic synthesis and HPLC analysis of the stereoisomers of miyakosyne A [(4E,24E)-14-methyloctacosa-4,24-diene-1,27-diyne-3,26-diol], a cytotoxic metabolite of a marine sponge Petrosia sp., to determine the absolute configuration of its major component as 3R,14R,26R

Six samples [(3R,14R,26R)-, (3R,14S,26R)-, (3S,14R,26S)-, and (3S,14S,26S)-1, a mixture of (3R,14R,26S)- and (3S,14R,26R)-1, and a mixture of (3R,14S,26S)- and (3S,14S,26R)-1] of miyakosyne A [1, (4E,24E)-14-methyloctacosa-4,24-diene-1,27-diyne-3,26-diol] were synthesized starting from the enantiomers of citronellal (2), employing olefin cross metathesis and R-selective asymmetric acetylation of a stereoisomeric mixture of acetylenic alcohols with vinyl acetate and lipase PS as key reactions. Separation of the eight stereoisomer of 1 by reversed phase HPLC at −56 °C was achieved after their esterification with (1R,2R)-2-(anthracene-2,3-dicarboximido)cyclohexanecarboxylic acid (16), and the natural miyakosyne A was found to be a mixture of 95.7% of (3R,14R,26R)-1 and 4.3% of (3R,14S,26R)-1. This is different from the (3R,14S,26R)-configuration of 1 as tentatively assigned by X-ray analysis.     

Determination of the absolute stereochemistry of lupane triterpenoids by fucofuranoside method and ORD spectrum

The absolute configurations of the secondary alcohols at C-3 position in betulinic acid and 3-epibetulinic acid have been unambiguously determined as S- and R-configurations, respectively, based on the fucofuranoside method. The absolute stereochemistry of 3α, 27-dihydroxylupen-20(29)-en-28-oic acid methyl ester, a potent topoisomerase II inhibitor, was determined to be 3R, 5R, 8R, 9R, 10R, 13R, 14S, 17S, 18R, and 19R by NMR and ORD spectroscopic studies.     

Polyhydroxylated pyrrolizidines. Part 4: Total asymmetric synthesis of unnatural hyacinthacines from a protected derivative of DGDP

(1R,2R,3S,5R,7aR)-1,2-Dihydroxy-3-hydroxymethyl-5-methylpyrrolizidine [(+)-3-epi-hyacinthacine A₃] 1 and (1R,2R,3S,7aR)-1,2-dihydroxy-3-hydroxymethylpyrrolizidine [(+)-3-epi-hyacinthacine A₂] 2 have been synthesized by Wittig's methodology using aldehyde 6, prepared from (2R,3R,4R,5S)-3,4-dibenzyloxy-N-benzyloxycarbonyl-2′-O-tert-butyldiphenylsilyl-2,5-bis(hydroxymethyl) pyrrolidine 3 (a partially protected DGDP), and the appropriated ylides, followed by cyclization through an internal reductive amination process of the resulting α,β-unsaturated ketone 7 and aldehyde 8, respectively, and total deprotection.     

Modified synthesis of methyl (1R,2R,3E,5R)-3-(hydroxyimino)-5-methyl-2-(1-methylethyl)-cyclohexanecarboxylate from (R)-4-menthen-3-one

A modified stereospecific synthesis of potentially biologically and pharmacologically active methyl (1R,2R,3E,5R)-3-(hydroxyimino)-5-methyl-2-(1-methylethyl)cyclohexanecarboxylate from (R)-4-menthen-3-one was developed using sequential 1,4-conjugate addition of Norman reagent catalyzed by CuI?CBF₃?Et₂O?CCuCl₂ and ozonolysis?Creduction of the intermediate (R,R,R)-vinylmenthone by hydroxylamine hydrochloridein MeOH.     

Synthesis of the trichloroacetamide derivative of enantio-iso-ADDA methyl ester

The divergent syntheses of the trichloroacetamide derivatives of (2S,3R,8R,9R,4E,6E)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyl-decadenoic acid (enantio-iso-ADDA), and (2R,3R,8R,9R,4E,6E)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyl-decadenoic acid (enantio-ADDA), have been achieved. Our approach takes advantage of highly efficient non-aldol aldol, palladium catalysed aza-Claisen and cross-metathesis methodologies.     

Raman optical activity of tartaric acid and related molecules

The Raman optical activity spectra of (2R, 3R) (+)- and (2S,3S) (?)-tartaric acid, (2R, 3R) (+)-dimethyl tartrate, (2R,3R) (?)-2,3-butanediol and (2S, 3S) (+)-dibenzoyl tartaric acid are presented. A large couplet at about 500cm^?1 in the first three molecules, which probably originates in deformations of a chiral structural unit, might serve as an indicator of conformation and absolute configuration.     

Synthetic studies on homophymine A: stereoselective synthesis of (2R,3R,4R,6R)-3-hydroxy-2,4,6-trimethyloctanoic acid

An efficient and highly stereocontrolled synthesis of (2R,3R,4R,6R)-3-hydroxy-2,4,6-trimethyloctanoic acid, the β-hydroxy acid unit that acylates the N-terminus of homophymine A, has been devised starting from iodoethane and (S,S)-pseudoephedrine propionamide in 9 steps and 36% average overall yield. Comparison of the ¹H and ¹³C NMR and optical rotation data of the resulting β-hydroxy acid with the natural fragment unambiguously verifies the configurational assignment as (2R,3R,4R,6R).     

The absolute configuration of the palmarumycins C9, C10, and C12 by quantum-mechanical calculations of CD spectra

The absolute configurations of the palmarumycins C₉ 1a, C₁₀ 2, and C₁₂ 3 were assigned by comparison of the quantum-mechanically calculated with the experimental CD spectra as (2R,3S,4aS,8aR), (2R,3R,4S,4aS,8aR), and (2R,3R,4R), respectively.     

Stereocontrolled transformation of nitrohexofuranoses into cyclopentylamines via 2-oxabicyclo[2.2.1]heptanes. Part 6: synthesis and incorporation into peptides of the first reported 2,3-dihydroxycyclopentanecarboxylic acid

Herein we report the intramolecular alkylation of nitronates of methyl-5-O-benzyl-3,6-deoxy-6-nitro-β-d-glucofuranoside and methyl-5-O-benzyl-3,6-deoxy-6-nitro-α-d-glucofuranoside into the corresponding 2-oxabicyclo[2.2.1]heptane derivatives. Similarly, methyl-3-O-benzyl-5-deoxy-5-nitromethyl-β-d-xylofuranoside and methyl-3-O-benzyl-5-deoxy-5-nitromethyl-α-d-xylofuranoside were cyclized to (1R,3R,4S,5R,7R)-7-benzyloxy-3-methoxy-5-nitro-2-oxabicyclo[2.2.1]heptane and (1R,3S,4S,5R,7R)-7-benzyloxy-3-methoxy-5-nitro-2-oxabicyclo[2.2.1]heptane, respectively. These 2-oxabicyclo[2.2.1]heptane derivatives were eventually transformed into enantiopure methyl (1S,2S,3R,4S,5R)-2-amino-2,3-dihydroxycyclopentanecarboxylate and this novel β-amino acid was incorporated into peptides.     

Enantiomerically pure 4-amino-1,2,3-trihydroxybutylphosphonic acids

(1S,2R,3S)-, (1R,2R,3S)- and (1S,2R,3R)-4-amino-1,2,3-trihydroxybutylphosphonic acids were synthesised. The synthetic strategy involved preparation of the respective 4-azido-2,3-O-isopropylidene-l-threose or -d-erythrose, addition of dialkyl phosphites, separation of C-1 epimeric O,O-dibenzyl phosphonates, the reduction of azides and the removal of the protecting groups. The (2R,3S) and (2R,3R) configurations in the final products were secured by employing diethyl l-tartrate and d-isoascorbic acid as starting materials. The stereochemical course of the addition to the carbonyl groups in 4-azido-2,3-O-isopropylidene-l-threose or -d-erythrose followed that established earlier for 2,3-O-isopropylidene-d-glyceraldehyde and similar (3:1-4:1) diastereoselectivities were achieved.     

Synthesis of tripeptide hydrolysate from papuamide A: determination of absolute stereostructure of β-methoxytyrosine

Four diastereomers, (2R,3R), (2S,3S), (2S,3R) and (2R,3S) at β-methoxytyrosine (β-OMeTyr), of the tripeptide hydrolysate, H-(S)-N-MeThr-β-OMeTyr-(S)-Hpr-OH, from papuamide A have been synthesized. Comparison of the ¹H NMR data of the natural hydrolysate with the four synthetic diastereomers unambiguously establishes the relative and absolute stereochemistry of the methoxytyrosine as 2R,3R.     

Studies on the transformation of nitrosugars into iminosugars III: synthesis of (2R,3R,4R,5R,6R)-2-(hydroxymethyl)azepane-3,4,5,6-tetraol and (2R,3R,4R,5R,6S)-2-(hydroxymethyl)azepane-3,4,5,6-tetraol

A divergent synthesis of the two novel polyhydroxylated azepanes (2R,3R,4R,5R,6R)-2-(hydroxymethyl)azepane-3,4,5,6-tetraol and (2R,3R,4R,5R,6S)-2-(hydroxymethyl)azepane-3,4,5,6-tetraol from d-mannose is described. The method involves a Henry reaction between dimethyl-tert-butylsilyl 2,3-O-isopropylidene-α-d-lyxo-pentodialdo-1,4-furanoside and 2-nitroethanol followed by a reductive ring closure of the resulting epimeric nitro aldols. Glycosidase inhibition tests showed that (2R,3R,4R,5R,6S)-2-(hydroxymethyl)azepane-3,4,5,6-tetraol exhibits a weak but selective inhibition against α-l-fucosides.     

Stereospecific microbial reduction of ethyl 1-benzyl-3-oxo-piperidine-4-carboxylate

Microbial reduction of ethyl 1-benzyl-3-oxo-piperidine-4-carboxylate by the majority of evaluated microorganisms gave the ethyl cis-(3R,4R)-1-benzyl-3R-hydroxy-piperidine-4R-carboxylate as the major product in high diastereo- and enantioselectivities. The 3R,4R-hydroxy ester was produced in 97.4% diastereomeric excess (de) and 99.8% enantiomeric excess (ee) by Candida parapsilosis SC16347, while 99.5% de and 98.2% ee were obtained from reduction by Pichia methanolica SC16415. A few of the evaluated microorganisms gave 10–40% of the ethyl trans-(3R,4S)-1-benzyl-3R-hydroxy-piperidine-4S-carboxylate as the minor product.     

New asymmetric strategy for the total synthesis of naturally occurring (+)-alexine and (−)-7-epi-alexine

A novel and highly convenient process is described for the asymmetric synthesis of polyhydroxylated pyrrolizidine alkaloids, (+)-alexine [(1R,2R,3R,7S,7aS)-3-hydroxymethyl-1,2,7-trihydroxypyrrolizidine] and (−)-7-epi-alexine [(1R,2R,3R,7R,7aS)-3-hydroxymethyl-1,2,7-trihydroxypyrrolizidine], as the potent glycosidase inhibitors by featuring the efficient and stereodefined elaboration of the functionalized pyrrolidine derivatives, which were, in turn, prepared via stereoselective manipulation of the homochiral allyl alcohol precursors derived from l-xylose.     

Chiral terpene auxiliaries IV: new monoterpene PHOX ligands and their application in the catalytic asymmetric transfer hydrogenation of ketones

New PHOX ligands, derived in three steps from (1R,2S,3R,5R)-3-amino-apopinan-2-ol 1 and (1R,2R,3S,5R)-3-amino-pinan-2-ol 2 were applied as chiral ligands for the formation of ruthenium catalysts. The catalysts were used in asymmetric transfer hydrogenations of prochiral ketones producing the corresponding alcohols in moderate to high yields and enantioselectivity.