Synthetic studies toward potent cytostatic macrolide rhizopodin: stereoselective synthesis of the C16-C28 fragment

A stereoselective synthesis of the C16-C28 fragment of cytostatic C₂-symmetric macrolide rhizopodin is described. Enantioselective addition of a chiral thiazolidinethione derived titanium enolate to acetal, Evans’ aldol reaction, Horner-Wadsworth-Emmons reaction, and Mukaiyama aldol reaction were applied as key steps.     

Synthetic studies on carbapenem antibiotics from penicillins. III. Stereoselective radical reduction of a chiral 3-isocyanoazetidinone: a total synthesis of optically active carpetimycins2

A new, efficient synthesis of the optically active carpetimycins $\text{1}$ from penicillins has been achieved via, as key steps, aldol reaction of isonitrile $\text{19}$, followed by n-Bu₃SnH reduction.     

Convergent synthesis of panclicin-D via intramolecular SN2 displacement approach

A convergent enantioselective synthesis of panclicin-D has been reported from simple octanal using syn aldol reaction via intramolecular S_N2 displacement reaction for the first time towards the construction of anti-β-lactones in panclicin-D. The key steps involved are C-allylation, asymmetric aldolization under Crimmins condition, intramolecular S_N2 displacement, and Mitsunobu esterification reaction.     

Stereoselective synthesis of the C14-C26 fragment of the cytotoxic macrolide FD-891

A stereoselective synthesis of the C₁₄-C₂₆ fragment of the naturally occurring, cytotoxic macrolide FD-891, is described. Asymmetric Evans aldol reactions and aldehyde Brown allylations are key steps of the synthesis.     

A Baylis-Hillman approach to the synthesis of C1-C11 fragment of caribenolide I

Stereoselective synthesis of C₁-C₁₁ fragment of caribenolide I, a potent antitumour macrolide isolated from a marine dinoflagellate Amphidinium sp. is described. The key steps rely on asymmetric aldol reactions, to control the absolute configurations of C₂, C₃ and C₁₀ stereogenic centres.     

An aldol approach to the synthesis of the anti-tubercular agent erogorgiaene

A total synthesis of erogorgiaene is described in 16 steps. The synthesis relies upon a highly diastereoselective intramolecular Friedel-Crafts reaction of an oxetane derived via an asymmetric syn aldol coupling.     

Stereoselective total synthesis of (+)-polyrhacitide A

A facile stereoselective total synthesis of secondary metabolite (+)-polyrhacitide A is described. Stereoselective aldol reaction, Horner-Wardsworth-Emmons reaction, Evans acetal intramolecular oxa-Michael reaction and diastereoselective syn reduction reaction are the key steps involved in the target synthesis.     

First total synthesis of rhuscholide A,glabralide B and denudalide

The first total synthesis of rhuscholide A, a benzofuran lactone possessing anti-HIV-1 activity, had been accomplished in 14 linear steps with 10.6% overall yield. In this synthesis, base-mediated phenol ortho-alkylation and piperidine promoted aldol condensation were exploited as key steps. The synthesis was flexible and allowed for the convenient preparation of two analogous natural products glabralide B and denudalide.     

Enantioselective Total Synthesis of (+)‐Steenkrotin A and Determination of Its Absolute Configuration

The first enantioselective total synthesis of (+)‐steenkrotin A has been achieved in 18 steps and 4.2 % overall yield. The key features of the strategy entail a Rh‐catalyzed O?H bond insertion followed by an intramolecular carbonyl‐ene reaction, two sequential SmI₂‐mediated Ueno–Stork and ketyl–olefin cyclizations, and a cascade intramolecular aldol condensation/vinylogous retro‐aldol/aldol process with inversion of the relative configuration at the C7 position. The absolute configuration of (+)‐steenkrotin A was determined based on the stepwise construction of the stereocenters during the total synthesis.     

Synthesis of southern (C1′-C11′) fragment of pamamycin-635A

The synthesis of the southern (C1′-C11′) fragment of pamamycin-635A, isolated from Streptomyces alboniger, was achieved via an Evans aldol reaction, a cis-selective iodoetherification and a stereospecific deiodination as the key steps.     

Concise Total Synthesis of Ieodomycin A and B

A concise total synthesis of ieodomycin A and B was achieved in six and seven steps respectively from commercially available geraniol, which involved the construction of the C-5 hydroxyl via an Ti(OⁱPr)₄/(S)-BINOL-mediated asymmetric aldol reaction as the key step.     

Asymmetric synthesis of a potent azepanone-based inhibitor of the cysteine protease cathepsin K

In this account we detail the asymmetric synthesis of 1, a potent azepanone-based inhibitor of cathepsin K (K_i = 0.16 nM), which has been shown to inhibit the production of biomarkers of bone resorption in monkeys. The key steps in the synthesis sequence were the utility of the Evans aldol reaction coupled with the ring closing olefin metatheses to assemble the azepanone core contained within 1.     

Total syntheses of 28,29-diepi-arenamide A, 29-epi-arenamide A, and 28-epi-arenamide A

This communication describes the synthesis of stereochemical analogs of arenamide A, a 19-membered cytotoxic depsipeptide isolated from the fermentation broth of a marine bacterial strain Salinispora arenicola. The key steps are diastereoselective aldol reaction, Mitsunobu reaction, and HATU mediated macrolactamization.     

Application of oxetane ring opening toward stereoselective synthesis of zincophorin fragment

A stereoselective synthesis of the C1–C11 fragment of zincophorin was achieved by using an intramolecular oxetane ring opening reaction as the key step. The oxetane moiety was synthesized by employing a desymmetrization protocol developed at our group and a non-Evans syn aldol as the key steps toward the synthesis.     

Synthesis of both enantiomers of conosilane A

Conosilane A, an inhibitor of 11β-hydroxysteroid dehydrogenase type 1 isolated from Conocybe siliginea, is a tremulane sesquiterpene with highly oxygenated tetracyclic ring system. In this study, we report the synthesis of both enantiomers of conosilane A. The key steps of this synthesis involve asymmetric aldol reaction, furan-ring oxidation followed by transacetalization and intramolecular reductive Heck-type cyclization.     

Total Synthesis of (−)-Bafilomycin A1: Application of Diastereoselective Crotylboration and Methyl Ketone Aldol Reactions

A careful orchestration of protecting groups is an essential requirement for the total synthesis of the macrolide antibiotic bafilomycin A₁ ( 1 ). Key steps were the Suzuki cross-coupling reaction of two advanced, suitably protected intermediates prior to closure of the macrocycle, as well as a highly stereoselective methyl ketone aldol reaction.     

Studies on the total synthesis of sanglifehrin A: stereoselective synthesis of the C(29)-C(39) fragment

A highly stereoselective synthesis of the C(29)-C(39) fragment of the potent immunosuppressant sanglifehrin A has been accomplished by a sequence involving 16 steps (18% overall yield) from N-propionyloxazolidinone 9. Key steps are a diastereoselective hydroboration, and a diastereoselective epoxidation of an allylic alcohol followed by a 1,5-anti boron-mediated aldol reaction of methyl ketone 4 with chiral aldehyde 5.     

Efficient total synthesis of manzacidin B

The highly diastereoselective synthesis of the marine natural product, (?)-manzacidin B, is described. A novel copper-catalyzed aldol reaction of the α-methylserine-derived aldehyde with an isocyanoacetate possessing (1R)-camphorsultam as the chiral auxiliary proceeded in a highly diastereoselective manner to give the (4R,5R,6R)-adduct, which was converted into manzacidin B in a few steps.     

1,4-Asymmetric induction in the titanium-mediated aldol reactions of α-benzyloxy methyl ketones

Good levels of 1,4-anti asymmetric induction are obtained in the TiCl₃(i-PrO)-mediated aldol reaction of α-benzyloxy methyl ketones with achiral aldehydes. Such methodology represents a new approach to the substrate-controlled acetate aldol reaction, which can be useful to design more efficient synthesis.     

Stereoselective total synthesis of (+)-(6R,2′S)-cryptocaryalactone and (−)-(6S,2′S)-epi cryptocaryalactone via asymmetric acetate aldol reaction

The total synthesis of (+)-(6R,2′S)-cryptocaryalactone and (?)-(6S,2′S)-epi cryptocaryalactone is reported based on asymmetric acetate aldol reaction. Still–Gennari reaction, Evans acetal intramolecular oxa-Michael reaction and lactonisation are the key steps in the target synthesis.