Zhuo-Ya Mao

Divergent Method to trans-5-Hydroxy-6-alkynyl/alkenyl-2-piperidinones: Syntheses of (−)-Epiquinamide and (+)-Swainsonine

An efficient diastereoselective approach to access trans-5-hydroxy-6-alkynyl/alkenyl-2-piperidinones has been developed through nucleophilic addition of α-chiral aldimines using alkynyl/alkenyl Grignard reagents. The diastereoselectivity of alkenyl in C-6 position of 2-piperidinone was controlled by α-alkoxy substitution, while the alkynyl was controlled by the coordination of the α-alkoxy substitution and stereochemistry of sulfinamide. The utility of this straightforward cascade process is demonstrated by the asymmetric synthesis of the (-)-epiquinamide and (+)-swainsonine.

Stereoselective formation of chiral trans-4-hydroxy-5-substituted 2-pyrrolidinones: syntheses of streptopyrrolidine and 3-epi-epohelmin A

A highly diastereoselective approach for the synthesis of trans-4-hydroxy-5-substituted 2-pyrrolidinones has been developed through an intramolecular cascade process of α-chiral aldimines using alkyl, aryl, alkynyl, and alkenyl Grignard reagents. The stereochemistry at the C-5 position of 2-pyrrolidinone after reaction with alkyl, aryl, and alkenyl Grignard reagents was solely controlled by α-alkoxy substitution. For alkynyl Grignard reagents, the stereochemistry was controlled by coordination of the α-alkoxy substitution and the stereochemistry of the sulfinamide. The utility of this one-pot cascade protocol is demonstrated by the asymmetric synthesis of streptopyrrolidine 5 and 3-epi-epohelmin A 3-epi-6.

Asymmetric syntheses of epohelmins A and B by In-mediated allylation

A diastereoselective new approach for the synthesis of trans-4-hydroxy-5-allyl-2-pyrrolidinone 9 has been developed through In-mediated allylation of α-chiral aldimine 8 with allyl bromide. The stereochemistry at the C-2 stereogenic center of 9 was controlled by both the α-OTBS substitution and the sulfinamide moiety. The utility of this asymmetric allylation is demonstrated by the asymmetric syntheses of epohelmins A (4) and B (10).

Divergent Synthesis of Revised Apratoxin E, 30-epi-Apratoxin E, and 30S/30R-Oxoapratoxin E

In this report, originally proposed apratoxin E (30S-7), revised apratoxin E (30R-7), and (30S)/(30R)-oxoapratoxin E (30S)-38/(30R)-38 were efficiently prepared by two synthetic methods. The chiral lactone 10, recycled from the degradation of saponin glycosides, was utilized to prepare the key nonpeptide fragment 9. Our alternative convergent assembly strategy was applied to the divergent synthesis of revised apratoxin E and its three analogues. Moreover, ring-closing metathesis (RCM) was for the first time found to be an efficient strategy for the macrocyclization of apratoxins.

Regio- and Stereoselective Cascades via Aldol Condensation and 1,3-Dipolar Cycloaddition for Construction of Functional Pyrrolizidine Derivatives

An efficient and step-economical approach to access functionalized pyrrolizidine derivatives by a one-pot tandem sequence, including an aldol condensation and subsequent 1,3-dipolar cycloaddition process, has been developed, starting from acetone, aldehyde, and proline. A number of substituted aromatic aldehydes were amenable to this transformation, and the desired products, racemic 7a-7w and chiral 9a-9m, were obtained with excellent regioselectivities and outstanding diastereoselectivities. Moreover, in situ NMR studies revealed MgSO4 could effectively promote the aldol condensation pathway in this tandem process.