A Scalable Synthesis of 1-Cytosinyl-N-malayamycin A:  A Potent Fungicide

Abstract

A stereocontrolled synthesis of 1-cytosinyl-N-malayamycin A, an N-analogue of the naturally occurring malayamycin A with fungicidal activity, is reported. The approach was designed to rely solely on substrate control for introduction of the required stereochemistry, avoiding the use of chiral reagents or auxiliaries. Formation of the N-nucleoside was achieved through the activation of a thioglycoside, proceeding via sulfonium and thionium intermediates. Ring closure metathesis was used to build the bicyclic perhydrofuropyran heterocycle.

Rational and Then Serendipitous Formation of Aza Analogues of Hoveyda-Type Catalysts Containing a Chelating Ester Group Leading to a Polymerization Catalyst Family

“…Olefin metathesis represents a powerful set of chemical transformations based on reacting olefins in the presence of transition-metal-containing catalyst that leads to the formation of new carbon–carbon double bonds . Not only has this reaction found many applications in modern organic synthesis carried out in academia but also most importantly it has been successfully applied by many branches of chemical industry as an effective tool for the preparation of pharmaceuticals, agrochemicals, flavor and fragrance components, transformation of biomass into valuable chemicals, and preparation of polymers . Importantly, in line with the current sustainability trends in industrial-scale synthesis, olefin metathesis can be efficiently conducted in environmentally friendly solvents without the protective atmosphere of an inert gas …”

Recent developments in the total synthesis of fungicidal natural products—a crop protection perspective

“…Contrary to this long list of inactive compounds, 1-cytosinyl-N-malayamycin (42) was shown to display a similar biological activity compared to malayamycin A (20) and a scalable synthetic access to 42 was developed. 15 In parallel to these chemical derivatizations, molecular modelling studies were performed starting from the available X-ray structure of 20. From both sides it became obvious that the orientation of the urea moiety in relation to the perhydrofuropyran and the methyl ether moieties was of key importance.…”

Synthesis and Biological Evaluation of 4′‐C,3′‐O‐Propylene‐Linked Bicyclic Nucleosides

“…The chiral starting material 21 was prepared on a large scale in 4 steps from a glucose derivative following known procedures. [18] Oxidative cleavage of the diol 21 by treatment with NaIO 4 in a mixture of dioxane and water furnished the aldehyde 22. Without isolation, treatment of the aldehyde 22 with excess formalScheme 3.…”

“…Reagents and conditions: (a) see ref. [18] dehyde and sodium hydroxide afforded the corresponding aldol, which was then trapped by reduction with sodium borohydride to yield the desired diol 23. [19] According to previously reported examples, the less hindered 5Јβ-hydroxy group of diol 23 was stereoselectively protected as a silyl ether in 64 % yield.…”