An enantioselective total synthesis of (+)-geissoschizine

[formula: see text] A concise asymmetric synthesis of the indole alkaloid (+)-geissoschizine (1) has been completed. The synthesis features the highly diastereoselective vinylogous Mannich reaction of 3 with 4 to give 5, which is elaborated into the key tetracyclic intermediate 7 in two steps. Following the stereoselective introduction of the ethylidene moiety to give 9, reduction of the lactam and radical decarboxylation via an acyl selenide gave 12, which was converted into (+)-geissoschizine by formylation. The synthesis requires only 11 chemical operations and proceeds in an overall yield of 17%.     

An enantioselective total synthesis of (+)-ricciocarpin A

[reaction: see text] Starting from 4,4-dimethyl-2-cyclohexenone, an efficient total synthesis of ricciocarpin A (1) in natural form has been accomplished.     

Highly enantioselective total synthesis of (+)-isonitramine

A new efficient enantioselective synthetic method of (+)-isonitramine is reported. (+)-Isonitramine was obtained in 12 steps (98% ee and 43% overall yield) from δ-valerolactam via enantioselective phase-transfer catalytic alkylation, Dieckman condensation, and diastereoselective reduction as key steps.     

Catalytic enantioselective total synthesis of (+)-torrubiellone C

Silyl-protected (R)-methyl 2-(hydroxymethyl)butanoate was obtained by an enantioselective Ir-catalyzed hydrogenation in high yield and selectivity. Elaboration of this building block via Takai and Stille reactions gave a protected hydroxy polyene chain, which was coupled to a 5-hydroxyphenyl-4-hydroxy-2-pyridone derivative by a modified Horner-Wadsworth-Emmons reaction. Deprotection gave synthetic (+)-torrubiellone C, which led to the assignment of the configuration of the natural product as (R).     

A highly enantioselective total synthesis of (+)-goniodiol

A high-yielding enantioselective total synthesis of the bioactive styryllactone (+)-goniodiol has been realised, starting from readily available (S)-glycidol. A key step is an oxygen-to-carbon rearrangement of a silyl enol ether linked via an anomeric centre, facilitating the rapid and diastereoselective construction of this functionalised system.     

An enantioselective synthesis of (+)-azimic acid

Herein we report a concise enantioselective synthesis of (+)-azimic acid starting from (5S,6S)-6-methyl-5-benzyloxy-2-piperidinone 8a, which was prepared from protected (S)-3-hydroxyglutarimide 6 according to a method recently disclosed in our laboratory. The key step is a stepwise regioselective reductive alkylation of the imide 10, which established the 2,6-cis-stereochemistry in excellent diastereoselectivity.     

Two remarkable epimerizations imperative for the success of an asymmetric total synthesis of (+)-aigialospirol

Two remarkable epimerization processes were uncovered during our pursuit of an enantioselective synthesis of(+)-aigialospirol featuring a cyclic acetal tethered ring-closing metathesis.Through modeling,we were able to turn these two unexpected epimerizations to our advantage via modeling to ensure a successful and concise total synthesis,thereby firmly establishing cyclic acetal tethered RCM as a powerful strategy in natural product synthesis.Most importantly,calculations allowed us to fully understand the ...     

An organocatalytic enantioselective synthesis of (+)-duryne

An efficient enantioselective synthesis of the potent anticancer agent (+)-duryne was achieved by the use of a one-pot organocatalyzed hydroxylation/Ohira–Bestmann and Grubbs cross-metathesis/selective cis-Wittig reaction. This new approach is envisioned to facilitate the synthesis of every representative member of the family.     

Catalytic enantioselective total synthesis of (+)-dumetorine by ring-rearrangement metathesis

A concise, enantioselective synthesis of (+)-dumetorine is described, giving the natural product in six steps and a 27% overall yield from a readily available precursor. Among the key steps used, the synthesis entails a high-yielding ring-rearrangement metathesis (RRM), using the commercially available first generation Grubbs catalyst 2 in combination with Ti(Oi-Pr)₄ as a co-catalyst. This constitutes the first enantioselective total synthesis of the alkaloid from a known chiral intermediate, and hence a confirmation of its absolute stereochemistry.     

An expeditious enantioselective total synthesis of valilactone

The title compound was synthesized through an expeditious route using Crimmins aldolization to establish the two key stereogenic centers and a hydroxyl group activation (HGA) protocol to construct the anti alpha,beta-disubstituted beta-lactone from the corresponding syn aldol.     

An enantioselective total synthesis of pinnaic acid

An enantioselective and convergent total synthesis of marine natural product pinnaic acid has been achieved. Our general synthetic approach is featured with an asymmetric hydrogenation of racemic γ-keto ester 3, a diastereoselective methylation on the α-methylene of the (1R,5R)-lactone 4, and a diastereoselective Michael addition of the tertiary nitro cyclopentane. The central azaspiro[4.5]decane was constructed utilizing reductive cyclization of the δ-nitroketone followed by highly stereoselective reduction of the cyclic imine with NaBH₄. Ultimately, successive use of triethyl-2-phosphonopropionate and Heathcock's phosphorane 18 to elaborate C5 and C13 side chains completed the total synthesis of pinnaic acid.     

The catalytic enantioselective, protecting group-free total synthesis of (+)-dichroanone

Herein we report the first enantioselective total synthesis of (+)-dichroanone, confirming the absolute configuration of the natural product. This protecting group-free route features the first application of our enantioselective Tsuji allylation in the context of a natural product total synthesis. Additionally, this 11-step preparation of the molecule from commercial material features a novel Kumada-aromatization strategy and a rapid sequence for the conversion of a phenol to a hydroxy-p-benzoquinone.     

The first enantioselective total synthesis of(+)-preussin B and an improved synthesis of(+)-preussin by step-economical methods

The first enantioselective total synthesis of(+)-preussin B and an improved synthesis of the antifungal alkaloid(+)-preussin are described. Our approach relied on the four step-economical synthetic methods developed in our laboratory:(1) the cis-diastereoselective reductive dehydroxylation of hemiaminals;(2) the direct amide/lactam reductive alkylation;(3) the one-pot N,O-bisdebenzylation-N-methylation; and(4) the one-step synthesis of malimide from malic acid. Both total syntheses are quite concise, which have been achieved in six steps, and gave overall yields of 25.7% and 27.6%, respectively.     

Formal enantioselective synthesis of (+)-compactin

[reaction: see text] The challenging structural features and important biological activity of (+)-compactin (1) explain the substantial synthetic interest that it has generated. We report a novel enantioselective approach to the advanced intermediate 2a, which constitutes a formal synthesis of (+)-1. The sequence utilizes MacMillan's organocatalytic Mukaiyama-Michael reaction, which stereoselectively adds the silyloxyfuran 6 to alpha,beta-unsaturated aldehyde 7. The chirality generated in this reaction guides the formation of the other three consecutive stereocenters found in 2a.     

Straightforward enantioselective synthesis of (+)-ancistrofuran

This paper reports the straightforward enantioselective synthesis of (+)-ancistrofuran starting from a readily available enantiopure building block. A stereofacial directed diastereoselective addition of an organocerate for the installation of the required stereogenic center served as the key step. In addition, the efficient conversion of an intermediate hydroxy aldehyde to the one-carbon homologated cyanide was developed. The sequence was achieved by the mild formation of a cyanohydrin and the subsequent one-pot two-step Barton-McCombie double deoxygenation of the hydroxyl groups.     

Formal enantioselective synthesis of (+)-estrone

A formal total synthesis of (+)-estrone (4% overall yield; ca. 12 steps) could be achieved via the Torgov diene. An asymmetric allylic substitution is the key step for the construction of the chiral quaternary carbon center of a synthetic intermediate which was converted in four steps to the Torgov diene. [reaction: see text]     

An enantioselective total synthesis of aspergillides A and B

An enantioselective total synthesis of aspergillides A and B has been accomplished on the basis of a unified synthetic strategy that exploits stereodivergent intramolecular oxa-conjugate cyclization and Yamaguchi macrolactonization.     

Synthetic studies on cyathins: enantioselective total synthesis of (+)-allocyathin B2

[reaction: see text] The enantioselective total synthesis of (+)-allocyathin B(2) has been achieved. Our approach features a convergent enantioselective construction of the 5-6-7 tricyclic core system using the originally developed chiral building blocks via asymmetric catalysis, the intramolecular aldol reaction in high yield, successful samarium diiodide-mediated ring expansion, and a newly developed double-bond installation method.