Jianxian Gong

Total Synthesis of (±) Maoecrystal V

A concise first total synthesis of (±) maoecrystal V (1) is reported. The synthesis features a Wessely oxidative dearomatization of a phenol, an intramolecular Diels-Alder reaction, and a Rh-catalyzed O-H bond insertion as key steps.

Social regulation of aggression by pheromonal activation of Or65a olfactory neurons in Drosophila

When two socially naive Drosophila males meet, they will fight. However, prior social grouping of males reduces their aggression. We found olfactory communication to be important for modulating Drosophila aggression. Although acute exposure to the male-specific pheromone 11-cis-vaccenyl acetate (cVA) elicited aggression through Or67d olfactory receptor neurons (ORNs), chronic cVA exposure reduced aggression through Or65a ORNs. Or65a ORNs were not acutely involved in aggression, but blockade of synaptic transmission of Or65a ORNs during social grouping or prior chronic cVA exposure eliminated social modulation of aggression. Artificial activation of Or65a ORNs by ectopic expression of the Drosophila gene TrpA1 was sufficient to reduce aggression. Social suppression of aggression requires subsets of local interneurons in the antennal lobe. Our results indicate that activation of Or65a ORNs is important for social modulation of male aggression, demonstrate that the acute and chronic effects of a single pheromone are mediated by two distinct types of ORNs, reveal a behaviorally important role for interneurons and suggest a chemical method to reduce aggression in animals.

Diastereoselective Total Synthesis of (±)‐Schindilactone A

Schindilactone A (1) and structures 2–4 (Scheme 1a) are representative members of a novel group of nortriterpenoids isolated by Sun and co-workers from the plants of Schisandraceae, which have been used in China for the treatment of rheumatic lumbago and related diseases. Preliminary biological assays indicated that some of them possess biological activities for inhibiting hepatitis, tumors, and HIV-1. The synthetic challenge posed by 1 stems from the complexity of its molecular structure: a highly oxygenated framework bearing 12 stereogenic centers, eight of which are contiguous chiral centers located in the FGH tricyclic ring system, and an oxa-bridged ketal that lies within an unprecedented 7–8 fused carbocyclic core. The structural complexity together with the attractive biological activities has rendered 1 a target for synthetic studies. Herein we report our efforts on the development of synthetic methods and a strategy centered on the construction of the polycyclic ring system that allowed the first total synthesis of ( )-schindilactone A. This concise strategy opens a pathway for the syntheses of other compounds related to schindilactone A (2–4, Scheme 1a), as well as their derivatives and analogues.

Synthetic study toward the total synthesis of maoecrystal V.

A novel and concise approach for the construction of the core structure of maoecrystal V (1) has been developed. Utilizing the lead-mediated arylation of beta-ketoesters and oxidative dearomatization/IMDA reaction as key steps, the two consecutive all-carbon quaternary centers (C-9 and C-10) were constructed in a stereoselective manner. The developed chemistry paves the way for the total synthesis of this fascinating natural product.

Asymmetric total synthesis of (−)-lingzhiol via a Rh-catalysed [3+2] cycloaddition

The development of efficient reactions for the one-pot construction of bicyclic ring systems bearing two quaternary carbon centres at their bridgehead positions represents a significant challenge to synthetic chemistry. The development of new methods capable of overcoming this challenge is highly desirable, because this motif can be found in a wide range of natural products with significant biological activities. Herein, we report an efficient [3+2] cycloaddition reaction between an enal and an alleno rhodium species, which was generated in situ from the corresponding enynol via a retro metal-propargylation reaction, to give [3.3.0] and [3.4.0] bicyclic systems bearing two quaternary atoms at their bridgehead positions. The developed chemistry has been successfully applied to the asymmetric total synthesis of natural product (-)-lingzhiol (4) for the first time in 17 steps.

Tunable and chemoselective syntheses of dihydroisobenzofurans and indanones via rhodium-catalyzed tandem reactions of 2-triazole-benzaldehydes and 2-triazole-alkylaryl ketones.

Two novel rhodium(II)-catalyzed tandem reactions were developed for the synthesis of dihydroisobenzofuran and indanone derivatives from 2-triazole-benzaldehydes and 2-triazole-alkylaryl ketones. Dihydroisobenzofuran derivatives were obtained in good yields with high regioselectivities when alcohols were used as nuclophiles in these reactions, whereas the replacement of the alcohol with water resulted in the diastereoselective formation of highly functionalized indanone derivatives.

Direct construction of vicinal all-carbon quaternary stereocenters in natural product synthesis

Molecules containing vicinal all-carbon quaternary stereocenters are found in many secondary metabolites, and they exhibit a variety of biological and pharmacological activities. However, the construction of such a structural motif remains a significant challenge in natural product synthesis. Only in recent years have considerable efforts been made to construct vicinal quaternary stereocenters in a single-step operation. In this review, we focus on the different types of methods that have been successfully used in the total synthesis of natural products. Based on the classified reactions for the simultaneous generation of vicinal all-carbon quaternary stereocenters, the total syntheses of the natural products are discussed, placing emphasis on the diastereoselective preparation of vicinal quaternary carbon centers and the subsequent total syntheses.

Concise Stereoselective Synthesis of Oxaspirocycles with 1‐Tosyl‐1,2,3‐triazoles: Application to the Total Syntheses of (±)‐Tuberostemospiroline and (±)‐Stemona‐lactam R

A 4-substituted-1-tosyl-1,2,3-triazole-based stereoselective synthesis of structurally diverse oxaspirocycles is reported. The synthesis involves Rh-catalyzed loss of nitrogen from 4-substituted-1-tosyl-1,2,3-triazoles, Grignard reaction, and a ring-closing metathesis reaction as key steps. By employing readily available and stable 4-substituted-1-tosyl-1,2,3-triazoles as surrogates of diazo compounds and nitrogen sources, two types of oxaspirocycles were obtained. The latter compounds, which contain adjacent nitrogen stereocenters, could serve as the core structures of many natural products. This chemistry has been successfully applied to the total syntheses of (±)-tuberostemospiroline and (±)-stemona-lactam R.

Formal Total Synthesis of N-Methylmaysenine

A novel synthetic approach for the formal total synthesis of N-methylmaysenine (1) has been developed. Key steps involve the Ti-mediated vinylogous Mukaiyama aldol reaction of chiral ketene silyl N,O-acetal with beta-dithiane-substituted aldehyde, an aldol condensation, and a ring-closing metathesis reaction.

Isolation and Asymmetric Total Synthesis of Perforanoid A

A novel limonoid, perforanoid A, was isolated, and an asymmetric total synthesis was achieved in 10 steps. The key steps are chiral tertiary aminonaphthol mediated enantioselective alkenylation of an aldehyde to an allylic alcohol, Pd-catalyzed coupling of the allylic alcohol with vinyl ether to form the γ-lactone ring, and cyclopentenone ring formation through a Rh-catalyzed Pauson-Khand reaction. Preliminary studies show that perforanoid A is cytotoxic towards HEL, K562, and CB3 tumor cell lines.