Enantioselective synthesis of (−)-pinellic acid

An enantioselective convergent approach toward the total synthesis of pinellic acid 1 from 1,9-nonanediol is described. The synthetic strategy features iterative Sharpless asymmetric dihydroxylation, Sonogashira coupling and Birch reduction.     

Enantioselective formal total synthesis of (−)-trachyspic acid

An enantioselective formal total synthesis of (−)-trachyspic acid was carried out using, as key steps, an asymmetric aldol reaction of a chiral oxazolidinone and a diastereoselective alkylation of a chiral 1,3-dioxolan-2-one. The key lactone 3 was synthesized in five steps starting from dioxolanone 9.     

Enantioselective synthesis of (−)-idiospermuline

The enantioselective total synthesis of the nonacyclic polypyrrolidinoindoline (−)-idiospermuline is described. Stereocontrolled formation of the vicinal quaternary carbon centers is achieved in a single step by dialkylation of an unsymmetrical prostereogenic dienolate with a tartrate-derived chiral dielectrophile. A catalyst-controlled diastereoselective Heck cyclization is employed to form the diaryl-substituted quaternary center.     

Enantioselective total synthesis of (−)-microcarpalide

The enantioselective total synthesis of the actin-targeting metabolite (−)-microcarpalide is described. Key steps include ring-closing metathesis (RCM) for the final construction of the 10-membered lactone framework and stereoselective homologation of boronic esters for the insertion of all stereocentres with the desired absolute configuration. In particular, the acidic fragment was prepared in seven steps from a suitable chiral bromomethane boronate by means of two sequential stereoselective homologations to install the two stereocentres with the correct final R stereochemistry, employing (−)-pinanediol as the chiral director. Subsequent elaboration to the required C₇ backbone entailed nucleophilic displacement with a vinyl Grignard reagent, oxidative cleavage of the boronic scaffold and protection-deprotection manipulations. Interestingly, when the tribenzyloxy diene ester resulting from DCC-mediated coupling of the two key synthons was subjected to RCM in the presence of Grubbs' catalyst, the reaction proceeded stereoselectively to yield the desired trans oxecin-2-one, albeit with poor conversion.     

Enantioselective synthesis of (−)-barrenazines A and B

A short enantioselective synthesis of barrenazines A and B is described. Barrenazines A and B are prepared following a common synthetic route in nine steps (19% overall yield) and eight steps (21% overall yield), respectively, from readily available 4-methoxy-3-(triisopropylsilyl)pyridine. The synthesis relies on a highly diastereoselective nucleophilic addition of a Grignard reagent to a chiral acylpyridinium salt, a radical azidation of a silyl enol ether and the assembly of the pyrazine ring by reductive dimerization of a functionalized 5-azidopiperidin-4-one.     

Synthesis of (−)-galantinic acid via iterative hydrolytic kinetic resolution and tethered aminohydroxylation

A new synthetic strategy for (−)-galantinic acid is reported using iterative hydrolytic kinetic resolution and tethered aminohydroxylation as the key steps.     

Enantioselective synthesis of the carbocyclic moiety of (−)-carbovir

Enantioselective construction of the protected carbocycle moiety of the anti-HIV drug carbovir was achieved in 11 steps from (S)-(−)-ethyl lactate. The two key steps are a Claisen [3+3] sigmatropic rearrangement of (3S,4E)-3-(4-methoxy-phenoxymethyl)-hex-4-enoic acid dimethylamide and next, a ruthenium-catalysed ring closure metathesis leading to (1S,4S)-4-(4-methoxy-phenoxymethyl)-cyclopent-2-enol.     

Total synthesis of (−)-martinellic acid

An enantioselective formal total synthesis of the pyrrolo[3,2-c]quinoline natural product martinellic acid has been achieved. The key steps involve a Pd-catalyzed aryl amidation reaction of a pyrroglutamate derivative, an intramolecular [3+2] azomethine ylide-alkene cycloaddition and a reductive ring opening reaction.     

Enantioselective synthesis of the tricyclic core of (−)-FR901483

An enantioselective synthesis of the tricyclic core structure of the immunosuppressant natural product (−)-FR901483 has been achieved. A palladium-catalysed (Pd₂(dba)₃, Xantphos, KOPh) intramolecular enolate alkenylation reaction was used as the key ring forming step for the construction of the bicyclo-[3,3,1]-azanonane ring system. An alkylidene carbene 1,5-CH insertion reaction was used to construct the nitrogen-bearing stereocentre in the vinyl bromide cyclisation precursor.     

Enantioselective total synthesis of (S)-(−)-quinolactacin B

The enantioselective total synthesis of (−)-quinolactacin B (−)-1 was performed in seven steps and 33% overall yield from tryptamine. The synthesis features the use of ruthenium catalytic asymmetric hydrogen reaction to introduce the chirality in dihydro-β-carboline 2. Based on Noyori’s work, the hydrogenation using the (R,R)-TsDPEN-Ru complex produces dihydro-β-carbolines possessing the (S) absolute configuration, the corrected asymmetric center of the natural product. The synthetic quinolactacin B displayed optical rotations that was in accordance with that of the natural product, thereby supporting the (S) configuration for natural quinolactacin B. The final product’s stereochemical assignment is in agreement with that proposed by Nakagawa and co-workers.     

Enantioselective synthesis of (−)-α-conhydrine via cyclic sulfate methodology

An asymmetric synthesis of (−)-α-conhydrine is described using the Sharpless asymmetric dihydroxylation and the regiospecific nucleophilic opening of a cyclic sulfate as the key steps.     

Enantioselective synthesis of (-)-cis-clavicipitic acid

An enantioselective synthetic method for (-)-cis-clavicipitic acid (1) was reported. 1 was obtained in 10 steps (99% ee and 20% overall yield) from 1H-indole-3-carboxylic acid methyl ester (9) via asymmetric phase-transfer catalytic alkylation and diastereoselective Pd(II)-catalyzed intramolecular aminocyclization as key steps.     

Enantioselective synthesis of (-)-roccellaric acid

[reaction in text] A new strategy for the synthesis of anti-4,5-disubstituted gamma-butyrolactones starting from inexpensive furan-2-carboxylic methyl ester was developed. By applying this methodology, the enantioselective synthesis of (-)-roccellaric acid ((-)-17) was accomplished using a copper(I)-catalyzed asymmetric cyclopropanation, a tin(IV)-catalyzed retroaldol/lactonization sequence of cyclopropanols, and a ruthenium-catalyzed intermolecular metathesis reaction as key steps.     

Enantioselective syntheses of 3,4,5-trisubstituted γ-lactones: formal synthesis of (−)-blastmycinolactol

A kinetic resolution process of Rh-catalyzed intramolecular Alder-ene reaction is described along with the studies of the substrate scope and stereochemistry of this remarkably efficient process. 3,4,5-Trisubstituted γ-lactones were synthesized in high enantioselectivity (>99% ee) and efficiency. The formal asymmetric syntheses of (−)-blastmycinolactol and (+)-blastmycinone, degradation products of the macrocyclic dilactone (+)-antimycin, were reported to address the applications of this methodology.     

Enantioselective synthesis of R-(+)-α and S-(−)-α-lipoic acid

An efficient synthesis of α-lipoic acid from the readily available cis-2-butene-1,4-diol employing a Claisen orthoester rearrangement and Sharpless asymmetric dihydroxylation as the key steps, is described.     

Enantioselective divergent approaches to both (−)-platensimycin and (−)-platencin

Enantioselective divergent approaches to (−)-platencin and (−)-platensimycin have been developed. A rationally designed chiral synthetic intermediate, possessing a useful α,β-unsaturated sulfone functionality, which served as a masked ketone as well as a good Michael acceptor, was successfully prepared via the highly enantioselective catalytic asymmetric intramolecular cyclopropanation (CAIMCP) developed in our laboratory.     

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.     

Enantioselective synthesis of (R)-deoxydysibetaine and (−)-4-epi-dysibetaine

Enantioselective synthesis of (R)-deoxydysibetaine and (−)-4-epi-dysibetaine was achieved by employing a samarium iodide-promoted reductive carbon-nitrogen bond cleavage of a proline derivative, as a key reaction.     

Titanocene (III) chloride mediated radical induced synthesis of (−)-methylenolactocin and (−)-protolichesterinic acid

Enantioselective synthesis of two anti-tumor antibiotics, (−)-methylenolactocin and (−)-protolichesterinic acid, has been achieved through titanocene(III) chloride mediated radical cyclization reaction starting from commercially available d-mannitol. Titanocene(III) chloride (Cp₂TiCl) was prepared in situ from commercially available titanocene dichloride (Cp₂TiCl₂) and zinc dust in THF.     

Stereoselective synthesis of (−)-jimenezin

Total synthesis of jimenezin was achieved via radical cyclization of β-alkoxyacrylate and β-alkoxyvinyl sulfoxide intermediates and intramolecular olefin metathesis reaction.