Total synthesis of (+)-cystothiazole A

[structure: see text]. The total synthesis of cystothiazole A is described. Key steps of the synthesis include an Evans asymmetric catalytic aldol reaction, which established the required C4-C5 stereochemistry. The [2,4']-bis(thiazole) was obtained applying our methodology of electrophilic activation of amide. Semistabilized Wittig reaction between the phosphonium salt 3 and the aldehyde 2 afforded 1 in nine linear steps and 38% overall yield.     

1,4-Induction in aldol reactions of (tertiary α′-alkoxy)methyl ketones: synthesis of the C8–C11 stereotriad of ent-fostriecin

A diastereoselective, boron-mediated aldol process inspired by the natural product fostriecin is described. Using a tertiary α′-stereocenter as the induction element, aldol adducts are provided with high yields, good to excellent levels of diastereoselection, and broad substrate scope. An Evans–Tischencko reduction of the aldol adduct from cinnamaldehyde resulted in the C₈–C₁₁ stereotriad of ent-fostriecin.     

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.     

Synthesis of the spiro fused β-lactone-γ-lactam segment of oxazolomycin

An effective synthetic strategy for construction of the novel spiro-bicyclic β-lactone-γ-lactam system present in oxazolomycin has been demonstrated. The 3,4-disubstituted pyrrolidine ring system was constructed via an Evans aldol reaction. The spiro-β-lactone ring was elaborated from a gem-hydroxymethyl moiety that was successfully installed by an aldol followed by a crossed Cannizzaro reaction.     

NHC-catalysed retro-aldol/aldol cascade reaction enabling solvent-controlled stereodivergent synthesis of spirooxindoles

An N-heterocyclic carbene (NHC)-catalysed retro-aldol/aldol cascade reaction of spirooxindole-based β-hydroxyaldehyde has been developed. The ring opening-closure process enables the diastereodivergent synthesis of spirocyclopentaneoxindole products with four consecutive stereocenters by simply changing the reaction solvents (THF or DCE). The Michael/aldol/retro-aldol/aldol sequential protocol allows the diastereodivergent synthesis of spirocyclopentaneoxindoles from 3-substituted oxindole and α,β-unsaturated aldehyde under the relay catalysis of a chiral secondary amine and an NHC catalyst. Moreover, four stereoisomers of the product can be selectively provided by using different combinations of a chiral secondary amine and a solvent.     

First synthesis and determination of the absolute stereochemistry of iso-cladospolide-B and cladospolides-B and C

The syntheses of iso-cladospolide-B, cladospolide-B and cladospolide-C are reported with 4S,5S,11S-configuration. Of the three stereogenic centres, the C-4/C-5 vic-diol was created by Evans aldol condensation, while the C-11 stereocentre was created by Jacobsen’s method. The synthesis of cladospolides 1-3 defined the absolute stereochemistry of these natural products.     

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.     

The convergent synthesis of novel cytotoxic certonardosterol D2 from diosgenin

Certonardosterol D₂, a polyhydroxysterol isolated from starfish Certonardoa semiregularis with exceptionally potent antitumor activity, was stereoselectively synthesized from natural rich diosgenin via the protocol of Julia olefination and Evans aldol reaction.     

Highly enantio- and diastereoselective vinylogous aldol reaction by LiCl-assisted BINOL-titanium species

The first highly enantio- and diastereoselective vinylogous aldol reaction between propionyl acetate-derived Brassard's diene and aldehydes was accomplished by titanium-lithium combined Lewis acid, affording δ-hydroxy-γ-methyl-β-methoxy acrylates. This methodology was utilized in convenient and concise construction of the polypropionate moiety in cystothiazole A and melithiazole C.     

Stereoselective synthesis of the C(1)-C(13) segment of dolabelide B

The efficient construction of the C₁-C₁₃ segment of dolabelide B is described. A key element of the synthesis entails BITIP catalyzed asymmetric methallylation to establish the C₇ stereocenter, which was then used to direct the stereoselective installation of the C₉ and C₁₁ centers through Evans reduction and 1,5-anti aldol condensation, respectively.     

Stereoselective synthesis of syn-α-methyl-β-hydroxy esters

Boron enolates of an ethyl ketone structurally related to erythrulose react with achiral aldehydes in a highly stereoselective fashion to yield 1,2-syn/1,3-syn stereoisomers. Oxidative cleavage of the aldol adducts yields enantiopure O-formylated syn-α-methyl-β-hydroxy esters, easily cleaved to the corresponding hydroxyl-free compounds. The aforementioned ketone behaves therefore as a chiral propionate enolate equivalent.     

Synthesis of a fluoroalkene peptidomimetic precursor of N-acetyl-l-glutamyl-l-alanine

Fluoroolefin peptidomimetics of the dipeptide N-acetyl-Glu-Ala were synthesized via an Evans asymmetric aldol reaction and an Overman rearrangement. This dipeptide is the N-terminal of an octapeptide implicated in the signal transduction via PKCε.     

Practical asymmetric synthesis of β-hydroxy γ-amino acids via complimentary aldol reactions

Orthogonally protected chiral β-hydroxy-γ-amino acids can be accessed in >100 g quantities from readily available starting materials and reagents in three to four steps. These chiral synthons contain two adjacent stereocenters along with suitably protected functional groups (O-TBS, N-Boc) for downstream reactivity. Implementation of two existing aldol technologies allows rapid access to all possible stereoisomers of 1. The guiding principles during reaction optimization were reaction scalability and operational efficiency. Conversion of the amino acids to a variety of chiral building blocks in one to two steps demonstrates their synthetic utility.     

Access to a Stereoisomer Library of Solomonamide Macrocycles

In an attempt towards understanding stereo‐structure activity relationships (SSARs), we have prepared eight possible stereoisomers of solomonamide macrocycles, in particular, by changing the stereochemical pattern of non‐peptide fragment AHMOA. Here, we have demonstrated different ways to construct three contiguous chiral centers present in solomonamide B macrocycle using substrate/reagent‐controlled methods. These methods involve Brown crotylation, NHK reaction and Evans aldol addition as key steps to synthesize key non‐peptide fragment. Further, these non‐peptide fragments were converted to their corresponding macrocycles via ligand‐free intramolecular Heck reaction.     

An improved synthesis of (−)-brevisamide, a marine monocyclic ether amide of dinoflagellate origin

An improved synthesis of (−)-brevisamide a marine cyclic ether isolated from the red-tide dinoflagellate Karenia brevis was achieved. The ether ring portion was constructed from an unsaturated lactone, which was prepared enantioselectively via an Evans aldol reaction and one-pot lactonization in the presence of excessive base after an Ando reaction. The ether ring and a dienol side chain fragment were connected via Suzuki-Miyaura coupling.     

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.     

Synthesis and biological activity of mycalolide analogs

Mycalolide analog 4, consisting only of the side chain of mycalolide B (2), a trisoxazole macrolide of marine origin, was stereoselectively synthesized using Roush crotylboration, an Evans aldol reaction, and a Paterson aldol reaction as key steps. The analog 4 was found to have strong actin-depolymerizing activity.     

Asymmetric synthesis of (−)-chicanine using a highly regioselective intramolecular Mitsunobu reaction and revision of its absolute configuration

First asymmetric synthesis of (−)-chicanine has been accomplished in 14 steps by employing the Evans asymmetric syn-selective aldol reaction, diastereoselective hydroboration and an regioselective, intramolecular Mitsunobu etherification. The absolute configuration of (+)- and (−)-chicanine has been revised to 2R,3S,4R,5R and 2S,3R,4S,5S, respectively, through CD analysis.     

Towards a simplified peloruside A: synthesis of C1-C11 of a dihydropyran analogue

A simplified analogue of the C1-C11 fragment of peloruside A has been synthesised starting from a monoprotected 2,2-dimethylpropane-1,3-diol. Oxidation, asymmetric allylation and acryloylation provided a substrate for ring-closing metathesis to a δ-lactone. Reduction, acylation and homologation with trimethyl(vinyloxy)silane provided a protected C3-C11 analogue in a stereoisomer manner. Introduction of the C1-C2 fragment and incorporation of the 2,3-syn stereochemistry was achieved by a boron-mediated Evans aldol reaction.     

Highly stereoselective TiCl4-Catalyzed Evans-aldol and Et3Al-mediated Reformatsky reactions. Efficient accesses to optically active syn- or anti-alpha-trifluoromethyl-beta-hydroxy carboxylic acid derivatives

[reaction: see text] The TiCl(4)-catalyzed Evans-aldol reaction of optically active 3,3,3-trifluoropropanoic imide gave the non-Evans syn product stereoselectively, whereas the Reformatsky reaction of 2-bromo-3,3,3-trifluoropropanoic imide in the presence of Et(3)Al led to the Evans anti product. These new approaches enabled us to synthesize all stereoisomers of trifluoromethylated aldol products for the first time.