Synthesis of (+)-Hypoxylactone through Allenoate γ-Addition: Revision of Stereochemistry

Abstract

A synthesis of (+)-hypoxylactone has been accomplished in four steps starting from the allenoate γ-addition of threo-3-chloro-2-silyoxybutanals, leading to the revision of stereochemistry. The key was the discovery of control elements required to matching/mismatching cases in the allenoate γaddition to provide the desired adducts as a single isomer. The utility of the γ-adduct was demonstrated with the Au(I)-catalyzed cyclization to afford (+)-xylogiblactone A. Use of Ag 2 O was the key to epoxidation for preventing epimerization of the γ-lactone ring.

Marine natural products

“…339 The structure of (+)-hypoxylactone 870 originally obtained from a fungus isolated from mangrove driftwood, has been revised through total synthesis. 340…”

Deciphering the Chameleonic Chemistry of Allenols: Breaking the Taboo of a Onetime Esoteric Functionality

“…Both regiochemical and stereochemical outcomes of the reaction are explained through a Curtin-Hammet-type transition state 49 , selectively favoring γ-addition products 50 and providing excellent chiral and central enantioselectivities (Scheme ). The methodology was also applied for the kinetic resolution of racemic aldehydes, and further generation of the butenolide core of the natural product (+)-xilogiblactone A. − …”

Synthesis of (+)-Xylogiblactones B and C through a Kinetic Resolution of the Allenoate γ-Addition: Stereochemical Establishment

“…4 This effort has resulted in fruitful outcomes, demonstrating its utility not only in the synthesis of naturally occurring (+)-xylogiblactone A (1) with clarification of stereochemical relationship 4 but also in the correction of stereochemistry for (+)-hypoxylactone (2) (Figure 1). 5 In this respect, chemical synthesis was highlighted as having an important role to play in the structural elucidation of molecular architecture. 6 The remaining task for related γlactone polyketides, especially xylogiblactones B and C, is the development of practical synthetic pathways and the confirmation of their stereochemistry.…”

“…With this issue in mind, we set out to design a synthetic route for xylogiblactones B ( 3 ) and C ( 4 ) based on our previous studies (Scheme ). , Rapid construction of the stereochemical framework for (+)-xylogiblactone A ( 1 ) through the allenoate γ-addition of racemic aldehydes via novel kinetic resolution clearly demonstrates the efficient utility of this transformation . The distinct characteristic aspects of this approach, in terms of the unique stereoselective assembly and the structural features of the products, have prompted us to pursue further investigations, as depicted in Scheme .…”