Biogenetically-modelled total syntheses (−)-nocardicin A and (−)-nocardicin G

A protected form of L-seryl-D-(p-hydroxyphenyl)glycine was cyclized in a biogenetic sense and partially deprotected to give (−)-t-butyl 3-amino nocardicinate (5) from which (−)-nocardicin A (1) and (−)-nocardicin G (11) were prepared.     

Stereoselective total syntheses of (−)-pseudohygrophorone A12 and (−)-pseudohygrophorone B12

Abstract

Stereoselective total syntheses of anti-fungal cyclohexenones (?)-pseudohygrophorone A¹² and (?)-pseudohygrophorone B¹² were achieved. Salient features of these syntheses are the diastereoselective addition of dodecylmagnesium bromide to highly oxygenated ketone derived from (?)-quinic acid and α-oxidation of the enone.     

Short syntheses of (−)-clavaminol A and deacetyl (+)-clavaminol H

Concise stereoselective syntheses of (?)-clavaminol A and deacetyl (+)-clavaminol H have been achieved from simple starting materials. Highlights of the synthesis for (?)-clavaminol A include a highly diastereoselective chelation-controlled hydride reduction of an amino ketone to give the anti amino alcohol directly, and NaBH₄-mediated dehalogenation. The main synthetic approach for deacetyl (+)-clavaminol H features a highly diastereoselective chelation-controlled hydride reduction of the amino ketone to construct the anti amino alcohol and a palladium catalyzed hydrogenation reaction at the final step.     

Enantioselective syntheses of (+)- and (−)-brazilin

Two enantiomers of brazilin were prepared in 9 steps from 7-hydroxychroman-4-one using the AD-mix-α and AD-mix-β-directed enantioselective dihydroxylation of 3-(4-hydroxy-3-methoxyphenyl)-2H-chromen-7-ol as a key step.     

De novo asymmetric synthesis of (−)-nanaomycin A

The de novo asymmetric total synthesis of (?)-nanaomycin A is described. The entirely linear route required only 13 steps from commercially available starting materials (3% overall yield). Key transformations include a Claisen rearrangement, an asymmetric dihydroxylation, a regioselective tosylation, a diastereoselective intramolecular Friedel-Crafts alkylation and a nitrile hydrolysis. As the route relies on a Sharpless asymmetric dihydroxylation it is equally amenable for the synthesis of (+)-nanaomycin A.     

Enantioselective total syntheses of (−)-clavaminol A and deacetyl (+)-clavaminol H

An efficient enantioselective approach to the syntheses of (?)-clavaminol A and deacetyl (+)-clavaminol H is presented, starting from n-decanol. The synthesis features Sharpless asymmetric dihydroxylation (AD), regioselective epoxide formation/opening and α-tosylation as key steps.     

Expedient syntheses of indolizidines (−)-167B and (−)-209D

Indolizidine alkaloids (−)-167B and (−)-209D were synthesized via an expedient route using hydroacylation and amination.     

An efficient and practical asymmetric synthesis of (−)-tasimelteon

Tasimelteon is a useful drug for the treatment of Non-24 in totally blind individuals. An efficient and convenient asymmetric synthesis of tasimelteon has been developed from 4-vinyl-2,3-dihydrobenzofuran through six steps in 53% overall yield using the Corey–Bakshi–Shibata (CBS0 asymmetric reduction of ketone as a key step.     

A simple asymmetric synthesis of (+)- and (−)-2,6-diaminopimelic acids

The asymmetric synthesis of both the enantiomers of 2,6-diaminopimelic acid (2,6-DAP) has been accomplished starting from the chiral synthon 1.     

The total syntheses of (−)-indicine N-oxide and intermedine N-oxide

The total syntheses of (−)-indicine N-oxide, the enantiomer of natural indicine N-oxide and intermedine N-oxide have been achieved.     

Total synthesis and cytotoxicity of (−)-jorumycin and its analogues

(?)-Jorumycin and its 15 C-22 analogues were prepared employing l-tyrosine as the chiral starting material via 21 steps. These analogues, along with (?)-jorumycin itself, were evaluated in vitro for cytotoxicity against HCT-8, BEL-7402, Ketr3, A2780, MCF-7, A549, BGC-823, Hela, HELF, and KB cells. The IC₅₀ values of the cytotoxicity of most of these analogs were at the level of nM, which was similar to that of (?)-jorumycin. Among these analogs including (?)-jorumycin, hippuric acid ester derivative 23 exhibited the most potent and broad-spectrum cytotoxic activity against the ten cell lines with an average IC₅₀ of 2.12 nM.     

Catalytic asymmetric syntheses II. Hydrogenation of α,β-unsaturated ketones using chiral ruthenium complexes

α,β-Unsaturated ketones have been hydrogenated inthe presence of HRuCl-(TBPC)₂ (TBPC = (−)-trans-1,2-bis(diphenylphosphinomethyl)cyclobutane) to give ketones with a maximum optical purity of 62%. Factors affecting the stereoselectivity of the catalytic reaction are discussed.     

Total synthesis of (−)-vitrenal and its biological activity

(−)-Vitrenal, the enantiomer of a natural sesquiterpene aldehyde isolated from a liverwort, has been synthesized starting from (+)-Δ³-carene, and its activity as a plant-growth regulator has been tested.     

Electrophilic asymmetric syntheses of α-hydroxy carboxylic acids

Asymmetric electrophilic synthesis of α-hydroxy carboxylic acids from chiral amide derivatives of tert-butyl- and trialkylsilyl- protected glycolic and lactic acids are described which lead to chiral α-hydroxy carboxylic acids in 60–95% diastereomic excess.     

Total syntheses of macrosphelides (+)-A, (−)-A and (+)-E

Total syntheses of (+)-macrosphelide A 1 (18.5% overall yield in 11 steps) and (+)-macrosphelide E 2 (23.9% overall yield in 11 steps) have been achieved via the chemoenzymatic reaction product (4R,5S)-4-benzyloxy-5-hydroxy-2(E)-hexenoate 4. The enantiomer (−)-A (1) (14.2% overall yield in 11 steps) of (+)-1 was also synthesized from the chemoenzymatic reaction product (4S,5R)-4-benzyloxy-5-hydroxy-2(E)-hexenoate 4.     

Enantiodivergent syntheses of γ-substituted butenolides with tertiary and quaternary asymmetric centers

Continuous nucleophilic addition with several organometallic reagents to tricyclic lactone (−)-1 proceeded diastereoselectively. Newly generated tertiary and quaternary asymmetric centers were controlled by the order in which the nucleophilic reagents were added. Using this methodology, enantiodivergent syntheses of several γ-substituted butenolides with tertiary and quaternary asymmetric centers were established from a single chiral material.     

A convenient synthesis of (+)-albicanol based on enzymatic function: total syntheses of (+)-albicanyl acetate, (−)-albicanyl 3,4-dihydroxycinnamate, (−)-drimenol, (−)-drimenin and (−)-ambrox

By using lipase ‘PL-266’ from Alcaligenes sp. enantioselective acetylation of (±)-albicanol 4 with isopropenyl acetate gave the enantiomerically pure (+)-albicanyl acetate 3 and (+)-albicanol 4. Deprotection of (+)-3 afforded the natural (+)-albicanol 4 which was converted to the natural products (−)-albicanyl 3,4-dihydroxycinnamate 7, (−)-drimenol 8, (−)-drimenin 9 and (−)-ambrox 10.     

Protecting-group-free catalytic asymmetric total synthesis of (−)-rosmarinecine

The protecting-group-free asymmetric total synthesis of (?)-rosmarinecine was achieved in only four steps from the commercially available (±)-3-hydroxypyrrolidine hydrochloride (2a). The key steps include the direct oxidation of (±)-2a to (±)-3-hydroxy-1-pyrroline N-oxide (1a) using the Davis reagent and the domino reaction; viz., the lipase-catalyzed dynamic kinetic resolution of (±)-1a with 1-ethoxyvinyl ethyl maleate followed by the intramolecular [3+2] dipolar cycloaddition reaction of the generated optically active ester. Some insights into the mechanism of the racemization of the optically active 1a, observed during the enzymatic process, were also obtained.     

Catalytic, asymmetric synthesis of α-acetoxy amides

Non-racemic cyanohydrin acetates are readily available from aldehydes and potassium cyanide/acetic anhydride by use of bimetallic titanium (salen) catalyst 1. Treatment of the cyanohydrin acetates with a platinum(II) phosphinito catalyst 3 under neutral conditions results in chemoselective hydrolysis to the corresponding α-acetoxy amides in a racemization free process.