A concise diastereoselective approach to (+)-dexoxadrol, (−)-epi-dexoxadrol, (−)-conhydrine and (+)-lentiginosine from (−)-pipecolinic acid

A new diastereoselective pathway for the total synthesis of (+)-dexoxadrol, first asymmetric synthesis of (−)-epi-dexoxadrol and formal synthesis of conhydrine and (+)-lentiginosine is presented using commercially available (−)-pipecolinic acid. The key reactions utilized are Sharpless asymmetric dihydroxylation and Wittig reaction. The paper further describes the study of effect of protecting groups on dihydroxylation of a terminal olefin in piperidine ring system.     

Synthesis of polyhydroxylated indolizidines and piperidines from Garner's aldehyde: total synthesis of (−)-swainsonine, (+)-1,2-di-epi-swainsonine, (+)-8,8a-di-epi-castanospermine,pentahydroxy indolizidines, (−)-1-deoxynojirimycin, (−)-1-deoxy-altro-nojirimycin,and related diversity

Diastereoselective and diverse synthesis of polyhydroxylated indolizidines and piperidines have been described, where a common chiral intermediate 2-(hydroxymethyl) piperidine-3-ol is converted into (−)-swainsonine, (+)-1,2-di-epi-swainsonine, (+)-8,8a-di-epi-castanospermine, pentahydroxy indolizidines, (−)-1-deoxynojirimycin, (−)-1-deoxy-altro-nojirimycin, and related diversity. The key steps were hydroxy directed intramolecular aminomercuration, Mitsunobu cyclization, and diastereoselective dihydroxylation.     

A concise and stereoselective synthesis of (+)- and (−)-deoxoprosophylline

An efficient synthesis of (+)- and (−)-deoxoprosophylline was accomplished from the readily available cis-2-butene-1,4-diol in which the Sharpless asymmetric dihydroxylation was used as the key step.     

Chiral vicinal diols as platforms for separable diastereomers in Johnson-Claisen rearrangement: a new short route to (−)-nor-canadensolide, (−)-canadensolide and (−)-sporothriolide

The chiral vicinal diols prepared by asymmetric dihydroxylation in high enantioselectivities provide an excellent platform for separable diastereomers in the Johnson-Claisen rearrangement. The separated syn-diastereomers were converted into the advanced γ-(lactone-lactol) intermediates (in six steps, 26-27% overall yields) for the synthesis of (−)-nor-canadensolide, (−)-canadensolide and (−)-sporothriolide.     

Versatile synthesis of epicatechin series procyanidin oligomers, and their antioxidant and DNA polymerase inhibitory activity

Proanthocyanidins, known as condensed tannins or oligomeric flavonoids, exist in many edible plants and show various interesting biological activities. We have developed a simple and versatile method of synthesizing procyanidin oligomers consisting of (−)-epicatechin and (+)-catechin. This method is applicable to the synthesis of various 3-O-substituted oligomers. We report here the stereoselective and length controlled synthesis of [4-8]-condensed (−)-epicatechin series procyanidin oligomers. We described the details of the synthesis of an two tetramers, (−)-epicatechin-(−)-epicatechin-(−)-epicatechin-(−)-epicatechin and (−)-epicatechin-(−)-epicatechin-(−)-epicatechin-(+)-catechin (arecatannin A1), (−)-epicatechin pentamer and two 3,3″,3?-tri-O-galloyl trimers, (−)-epicatechin-(−)-epicatechin-(−)-epicatechin-3,3″,3?-tri-O-gallate and (−)-epicatechin-(−)-epicatechin-(+)-catechin-3,3″,3?-tri-O-gallate with the condensation method using TMSOTf as a catalyst. The ability of DPPH radical scavenging activity and DNA polymerase inhibitory activity of these oligomeric compounds were investigated.     

Total synthesis of the aromatase inhibitor dihydroisocoumarin via protective opening of lactones

Asymmetric total synthesis of a dihydroisocoumarin, (3R,4R)-(−)-6-methoxy-1-oxo-3-pentyl-3,4-dihydro-1H-isochromen-4-yl acetate (1) starting from commercially available m-anisic acid is described. Herein, we depict the use of protective opening of lactones and construction of δ lactone. The synthesis involves Wittig, Grubbs cross metathesis, and Sharpless dihydroxylation reactions.     

Scalable synthesis of (−)-trans-3-hydroxypipecolic acid via a useful chiral building block

A scalable synthesis of (−)-trans-2-(hydroxymethyl)-1,2,3,6-tetrahydropyridin-3-ol, a versatile chiral building block is described along with its transformation to (−)-trans-3-hydroxypipecolic acid.     

Synthesis of optically active seven-membered 1,5-anhydrocarbasugars and 1,4,5-tribenzoyloxy-2-ethoxy cycloheptanes via [5+2] cycloaddition

[5+2] Cycloaddition followed by asymmetric dihydroxylation procedure have been utilized to prepare novel cyclitols. Accordingly, rac-2α-hydroxy-6α-ethoxy-1,5-anhydro cyclohept-3-ene, 10 derived from [5+2] cycloaddition of 3-oxidopyrylium ylide and vinyl ether has been recognized as a seven-membered carbasugar equivalent and elaborated to 1,4,5-tribenzoyloxy-2-ethoxy cycloheptanes through a flexible, regio- and stereoselective strategy involving Sharpless asymmetric dihydroxylation conditions to resolve the compounds obtained. The structures and relative configurations of newly synthesized (+)-2α-acetoxy-6α-ethoxy-3β,4β-dihydroxy-1,5-anhydro cycloheptane ((+)-12)); (−)-1β,4β,5β-tribenzoyloxy-6α-ethoxy cycloheptane ((−)-17) and (+)-1α,4α,5α-tribenzoyloxy-6β-ethoxy cycloheptane ((+)-17) are unambiguously established by single crystal X-ray analysis and duly supported by ¹H and ¹³C NMR spectroscopy data.     

A new chiral diol derived from tetralone for the complexation of Lewis acids

A new approach to the rational design of Lewis acids based on face-face π-π interactions is described. The synthesis of two novel diols (−)(1R,3R)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalene-1,3-diol (−)-1 and (−)(1S,3R)-trans-2,2-dimethyl-1,2,3,4-tetrahydronaphthalene-1-3-diol (−)-9 is reported in six and five steps respectively starting from α-tetralone. Complexation of (−)(1R,3R)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalene-1,3-diol (−)-1 to phenylboronic acid shows the interplanar distance between the boron atom and the aromatic ring to be 3.05 Å, which is ideal for the proposed interactions.     

The first stereoselective total synthesis of (3S,4R)-dihydroxy-(6S)-undecyl-α-pyranone and total synthesis of (2S,3R,5S)-(−)-2,3-dihydroxytetradecan-5-olide

The first total synthesis of (3S,4R)-dihydroxy-(6S)-undecyl-α-pyranone 1 and total synthesis of (2S,3R,5S)-(−)-2,3-dihydroxytetradecan-5-olide 2 have been achieved in five steps in a highly stereoselective manner using Maruoka allylation, olefin cross-metathesis, and Sharpless asymmetric dihydroxylation as key steps.     

Stereoselective total synthesis of (+)-varitriol

Stereoselective total synthesis of (+)-varitriol, an antitumor natural product, was accomplished by two versatile strategies starting from the commercially available d-(−)-ribose and ethyl (S)-lactate. The key steps involved in the synthesis of the target molecule are epoxidation, cyclization, dihydroxylation and Diels-Alder reaction.     

Enantioselective, chemoenzymatic synthesis, and absolute configuration of the antioxidant (−)-gloeosporiol

The natural antioxidant (−)-gloeosporiol, isolated as a peracetylated derivative from a culture of the fungus Colletotrichum gloeosporioides, has been enantioselectively prepared from 3,4-dihydroxybenzaldehyde by means of a chemoenzymatic synthesis. The key intermediate was obtained by resolution with a lipase from Pseudomonas cepacia. Its stereochemistry, initially assigned as R, according to the Kazlaukas empirical rule for secondary alcohols, was independently confirmed by NMR and chirooptic methods. This, in turn, allowed the assignment of compound (−)-1 as (−)-(2S,3R,4R)-2-(3′,4′dihydroxyphenyl)tetrahydrofuran-3,4-diol.     

Asymmetric synthesis of (−)-acaterin

The asymmetric synthesis of (−)-acaterin, an inhibitor of acyl-CoA cholesterol acyl transferase has been achieved starting from the commercially available starting materials, octan-1-ol and methyl (R)-lactate. The key steps are a Sharpless asymmetric dihydroxylation and a Wittig olefination.     

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.     

Stereoselective synthesis of the C1-C20 segment of the microsclerodermins A and B

An enantioselective route for the synthesis of key fragment C1-C20 resident in microsclerodermins A and B is described. The route features deoxygenative rearrangement of an hydroxy-alkynoate and a highly enantio- and diastereo-controled iterative dihydroxylation as key reactions, starting from S-(−)-citronellol.     

An efficient and stereoselective synthesis of (3S,4R)-(−)-trans-4-(4′-fluorophenyl)-3-hydroxymethyl-N-methylpiperidine

An asymmetric conjugate addition reaction between a chiral α,β-unsaturated amido ester and ethyl-N-methylmalonamide has been used as a key step in the synthesis of (3S,4R)-(−)-trans-4-(4′-fluorophenyl)-3-hydroxymethyl-N-methylpiperidine, a key intermediate for (−)-paroxetine.     

Facile synthesis of (−)-tabtoxinine-β-lactam and its (3′R)-isomer

A concise and high yielding synthesis of (−)-tabtoxinine-β-lactam 1, the cause of tobacco wildfire disease, was achieved from l-serine using a zinc-mediated coupling reaction, Sharpless asymmetric dihydroxylation and lactamization of N-OBn amide as the key steps.     

The enantioselective synthesis of poison-frog alkaloids (−)-203A, (−)-209B, (−)-231C, (−)-233D, and (−)-235B″

The enantioselective synthesis of indolizidines (−)-203A, (−)-209B, (−)-231C, (−)-233D, and (−)-235B″ has been achieved and the absolute stereochemistry of both indolizidines 203A and 233D was established as 5S,8R,9S. The relative stereochemistry of natural 231C was established by the present asymmetric synthesis.     

Stereoselective synthesis of 1,4-dideoxy-1,4-imino-d-allitol and formal synthesis of (2S,3R,4S)-3,4-dihydroxyproline

A stereoselective synthesis of 1,4-dideoxy-1,4-imino-d-allitol 1 and formal synthesis of (2S,3R,4S)-3,4-dihydroxyproline was achieved via the addition of vinylmagnesium bromide to the benzylimine derived from (R)-2,3-O-isopropylidene glyceraldehyde followed by N-allylation, ring-closing metathesis (RCM), and dihydroxylation.     

Synthesis of a novel sphingosine kinase inhibitor (−)-F-12509A and determination of its absolute configuration

The synthesis of a novel sphingosine kinase inhibitor, (−)-F-12509A ((−)-1), was achieved in a highly efficient manner that included nine longest linear steps and 45% overall yield from (−)-bicyclic β-ketoester (−)-2, and its absolute configuration was determined to be (5S,9S,10S).