Asymmetric synthesis of (−)-(S,S)-homaline

The asymmetric synthesis of (−)-(S,S)-homaline was achieved in 8 steps from commercially available starting materials using the diastereoselective conjugate addition of the novel lithium amide reagent lithium (R)-N-(3-chloropropyl)-N-(α-methyl-p-methoxybenzyl)amide to methyl cinnamate to install the correct stereochemistry. Subsequent functional group manipulation of the resultant β-amino ester and Sb(OEt)₃-mediated macrolactamisation was followed by homodimerisation to give (−)-(S,S)-homaline in 18% overall yield, representing the first asymmetric, and by far the most efficient synthesis of this natural product reported to date.     

Rearrangement of N-alkyl 1,2-amino alcohols. Synthesis of (S)-toliprolol and (S)-propanolol

N-alkyl 1,2-amino alcohols were rearranged stereospecifically by using TFAA/Et₃N. This rearrangement has been used to synthesize N-isopropyl-3-(aryloxy)-2-hydroxypropylamines, β-adrenergic blocking agents such as (S)-toliprolol and (S)-propanolol.     

A practical enantioselective total synthesis of (−)-(S)-stepholidine

A convergent enantioselective total synthesis of (−)-(S)-stepholidine, a drug candidate for the treatment of schizophrenia and/or drug abuse, was described, which represented the first example of successful auxiliary-assisted Bischler–Napieralski cyclization of amide bearing bromine atom at 2-position of the C ring, followed by an introduction of the aryl methyl ester via Br–Li exchange. (−)-(S)-Stepholidine was synthesized in 6 steps, with 52% overall yield and >99% ee. The reported synthesis is practically free from chromatographic separation.     

Transformation of esters into allyl halides via substituted cyclopropanols. Application in the synthesis of (2S,3R,7R/S)-3,7-dimethyltridec-2-yl acetate and propionate, sex attractants of pine sawfly Diprion pini

A convenient new approach to the synthesis of the acetate and the propionate of (2S,3R,7R/S)-3,7-dimethyltridecan-2-ol, sex attractants of Diprion pini L., using the cyclopropanation of the ethoxycarbonyl group in O-THP protected ethyl (S)-lactate with ethylmagnesium bromide in the presence of titanium(IV) isopropoxide followed by C-2-C-3 cyclopropane ring opening as the key steps has been performed.     

A cyclopropanol approach to the synthesis of the C13-C21 fragment of epothilones from diethyl (S)-malate

A convenient new approach to the synthesis of the C13-C21 epothilone fragment using the cyclopropanation of the ethoxycarbonyl groups in O-THP protected diethyl (S)-malate with ethylmagnesium bromide in the presence of titanium(IV) isopropoxide followed by site-selective cyclopropane cleavage as the key steps has been performed.     

Short, stereoselective synthesis of C-glycosyl asparagines via an olefin cross-metathesis

The Grubbs second generation ruthenium catalyst was employed for the cross metathesis between α- and β-C-allyl glycosides and suitably protected l-vinyl glycines to furnish olefinic products in 57-94% yields. Hydrogenation afforded the C-glycosyl asparagines in high yield.     

Stereoselective synthesis of protected (2S,3S)-N-methyl-5-hydroxyisoleucine, a component of halipeptins

The stereocontrolled synthesis of the protected (2S,3S)-N-methyl-5-hydroxyisoleucine, a component of halipeptins A and B with potent anti-inflammatory activity, has been achieved. The key steps include (i) installation of a double bond to bicyclic lactam 4 using N-tert-butyl phenylsulfinimidoyl chloride, (ii) highly exo-selective Michael reaction with lithium dimethylcuprate in the presence of chlorotrimethylsilane, and (iii) Ru-catalyzed oxidative deprotection of N,O-benzylidene acetal to the acid anhydride.     

Biomimetically inspired total synthesis of (12S)-12-hydroxymonocerin and (12R)-12-hydroxymonocerin

A concise asymmetric total synthesis of (12S)-12-hydroxymonocerin (1) and (12R)-12-hydroxymonocerin (2) were efficiently achieved from the known 4-bromo-2,6-dimethoxyphenol. The synthetic approach was inspired by our biomimetic synthesis of (+)-monocerin (3) and 7-O-demethylmonocerin (4). The cis-fused furobenzopyranones of 1 and 2 was efficiently constructed via an intramolecular nucleophilic trapping of a quinonemethide intermediate, which was obtained by benzylic oxidation of compound 10 using 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ).     

A new synthetic approach for 4(S)-hydroxycyclopent-2-enone: a precursor to prostanoid synthesis

A new and efficient approach to 4(S)-hydroxycyclopent-2-enone is presented. This methodology allows the preparation of 4(S)-hydroxycyclopent-2-enone in large scale and with high optical purity.     

Ru-catalyzed enantioselective preparation of methyl (R)-o-chloromandelate and its application in the synthesis of (S)-Clopidogrel

The preparation of methyl (R)-o-chloromandelate via Ru-catalyzed asymmetric hydrogenation and transfer hydrogenation was investigated. With Ru-(R,R)-2,4,6-triisopropyl C₆H₂SO₂-DPEN as the catalyst and HCOOH-Et₃N azeotrope as the hydrogen donor, up to 92% ee was obtained in an optional condition. The synthesis of (S)-Clopidogrel was also studied.     

Biotransformation of (+)-(1R,2S)-fenchol by the larvae of common cutworm (Spodoptera litura)

Biotransformation of (+)-(1R,2S)-fenchol by the larvae of Spodoptera litura was carried out. Substrate was converted to three new terpenoids, (+)-(1R,2S)-10-hydroxyfenchol, (+)-(1R,2R,3S)-8-hydroxyfenchol and (−)-(1S,2S,6S)-6-exo-hydroxyfenchol, and one known terpenoid, (−)-(1R,2R,3R)-9-hydroxyfenchol. These structures were established by NMR, IR, specific rotation and mass spectral studies.     

A study of polychlorinated leucine derivatives: synthesis of (2S,4S)-5,5-dichloroleucine

The first total synthesis of (2S,4S)-5,5-dichloroleucine has been achieved in 11 steps from l-pyroglutamic acid. A key step is the dichlorination process on the hydrazone of aldehyde 13 with CuCl₂ in triethylamine.     

Synthesis and regioselective substitution of C-6 alkoxy derivatives of (S)-nicotine

Enantiopure (S)-6-alkoxynicotine derivatives have been synthesized in two steps from (S)-nicotine via (S)-6-iodonicotine. Deprotonation and substitution at the C-5 position of the pyridine ring of (S)-6-methoxynicotine were achieved using mesityllithium as the base at 0 °C. Conditions for the C-4 lithiation/substitution of (S)-6-isopropoxynicotine and (S)-5-chloro-6-methoxynicotine were also developed.     

An efficient asymmetric synthesis of (S)-2-cyclohexyl-2-phenylglycolic acid, the acid segment of oxybutynin

An innovative and facile synthesis of the title compound has been developed starting from (R)-cyclohexylidene glyceraldehyde. The key step in the synthesis is a chiral template-driven Grignard addition with absolute diastereocontrol. The other attractive features are the operational simplicity and the use of inexpensive compounds/reagents.     

A highly efficient stereoselective synthesis of (Z)- and (E)-allyl iodides from Baylis-Hillman adducts

A highly efficient synthesis of (Z)- and (E)-allyl iodides has been accomplished by treatment of Baylis-Hillman adducts with iodine and triphenylphosphine in methylene chloride at room temperature. The method is associated with mild reaction conditions, high yields and excellent stereoselectivity.     

Pheromone synthesis. Part 244: Synthesis of the racemate and enantiomers of (11Z,19Z)-CH503 (3-acetoxy-11,19-octacosadien-1-ol), a new sex pheromone of male Drosophila melanogaster to show its (S)-isomer and racemate as bioactive

The enantiomers of (11Z,19Z)-3-acetoxy-11,19-octacosadien-1-ol were synthesized from the enantiomers of 3,4-epoxy-1-butanol PMB ether. Its racemate was also synthesized. Its (S)-isomer and racemate were shown to possess the same pheromone activity as CH503, a long-lived inhibitor of male courtship in Drosophila melanogaster, although the racemate was less active.     

A concise enantioselective synthesis of l-(−)-733,061 and (2S,3S)-methyl 3-aminopiperidine-2-carboxylate using catalytic enantioselective aza-Henry reaction as key step

An efficient enantioselective synthesis of l-(−)-733,061 and (2S,3S)-methyl 3-aminopiperidine-2-carboxylate is accomplished by means of catalytic enantioselective aza-Henry reaction. A key feature of this protocol is organocatalysis as genesis of chirality to ensure high degree of distereo- and enantiocontrol.     

Enzyme-linked immunosorbent assay for the determination of 20(S)-protopanaxatriol

A highly sensitive and specific enzyme-linked immunosorbent assay (ELISA) method has been developed for the determination of 20(S)-protopanaxatriol (PPT), one of the major aglycones of dammarane-type ginseng saponins. Polyclonal antibodies raised against ginsenoside F₁ (GF₁)-bovine serum albumin showed high reactivities to PPT and GF₁, whereas they exhibited minor or even no cross-reactivities to other ginsenosides and protopanaxadiol (0.19%). The working range of this method extends from 50 pg ml⁻¹ to 20 ng ml⁻¹ of PPT. The assay reported here has been validated against an HPLC technique using PPT-containing samples and was shown to correlate closely (γ=0.993). This ELISA could be a useful tool for the determination of PPT contained in biological fluids and plant materials.     

Regio- and stereoselective 1(S)-camphorsulfonylation of monoalkoxycalix[4]arenes

The reaction of calix[4]arene monoalkyl ethers with 1(S)-camphor-10-sulfonyl chloride yields 1,2- or 1,3-alkoxy-1(S)-camphorsulfonyloxycalixarenes depending on the nature of the base used. In the presence of triethylamine only 1,3-substituted derivatives are formed. Two diastereomers of the 1,2-substituted calixarenes with clockwise and anticlockwise arrangement of alkyl and camphorsulfonyl groups at the narrow rim are formed in the presence of sodium hydride or potassium carbonate. Due to chiral induction of the camphorsulfonyl group the 1,2-substitution is diastereoselective. The ratio of diastereomers formed is dependent on the alkyl groups at the calixarene narrow rim.     

A stereoselective total synthesis of (−)-andrachcinidine via an olefin cross-metathesis protocol

A stereoselective total synthesis of 1-(2S,6R)-6-[(2S)-2-hydroxypentyl]-hexahydro-2-pyridinylacetone, (−)-andrachcinidine is reported. The strategy utilizes olefin cross-metathesis and intramolecular S_N2 cyclization as the key steps.