Chiron Approach to Formal Synthesis of 8,9-dideoxyneodysiherbaine (MSVIII-19)

Title:Chiron Approach to Formal Synthesis of 8,9-dideoxyneodysiherbaine (MSVIII-19)

Volume: 14 Issue: 4

Author(s): Alma Sanchez-Eleuterio, Virginia M. Mastranzo, Leticia Quintero and Fernando Sartillo-Piscil*

Affiliation:

• Centro de Investigación de la Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla (BUAP), 14 Sur Esquina San Claudio, San Manuel, 72570, Puebla,Mexico

Keywords: Chiron approach, dysiherbaine (DH), formal synthesis, hexahydrofuro[3, 2-b]pyran, MSVII-19, neodysiherbaine (NDH), ring closing metathesis, SHOWO.

Abstract: Background: The synthesis of biologically active model compounds represents a valuable tool for medicinal chemistry. In this regard, the synthesis of MSVII-19, a structurally simplified model compound of Dysiherbaine, developed by the group of Sasaki, was synthesized with the intention of preparing a powerful agonist or antagonist of glutamate receptor. Therefore, the synthesis of an advanced intermediate in the Sasaki’s synthesis of MSVIII-19 is reported.

Methods: Taking advantage of the furanose ring of the diacetone-D-glucose (DAG), the cis-fused hexahydrofuro[3,2-b]pyran ring system of the title compound was constructed by featuring two protocols: SHOWO (sequential hydrolysis-oxidation-Wittig olefination) and RCM (ring closing metathesis). Then, by applying a combined allylation at the anomeric position and a Pd-catalyzed double bond isomerization reaction, the methyl ester group in 1b was installed.

Results: The synthesis of an advanced intermediate of MSVIII-19 involves three key procedures: a) SHOWO (sequential hydrolysis-oxidation-Wittig olefination) protocol; b) RCM (ring closing metathesis) reaction; y c) the nucleophilic substitution at the anomeric position. Additionally, with the use of a cheaper starting material (DAG) than that used in the previous synthesis (tri-O-acetyl-D-glucal). The current synthesis is truly competitive with that reported by the Sasaki group.

Conclusion: A concise formal total synthesis of the advanced intermediate of MSVIII-19 was achieved. (Current synthesis: 14 steps; previous synthesis 20 steps).

Cite this article as:

Sanchez-Eleuterio Alma, Mastranzo M. Virginia, Quintero Leticia and Sartillo-Piscil Fernando*, Chiron Approach to Formal Synthesis of 8,9-dideoxyneodysiherbaine (MSVIII-19), Letters in Organic Chemistry 2017; 14 (4) . https://dx.doi.org/10.2174/1570178614666170307091943

DOI https://dx.doi.org/10.2174/1570178614666170307091943	Print ISSN 1570-1786
Publisher Name Bentham Science Publisher	Online ISSN 1875-6255