Synthesis of the spiroiminal moiety and approaches to the synthesis of marineosins A and B

Abstract

A short and efficient synthesis of model spiroiminals that have the same stereochemistry as marineosins A and B, but different conformations, was carried out in six or seven steps from 6-methyltetrahydropyran-2-one. These spiroiminals were also prepared biomimetically by reduction of an enol ether. A more highly substituted spiroiminal with the same stereochemistry and conformation as marineosin A was prepared in 11 steps from parasorbic acid. A macrocyclic pyrrole lactone was prepared stereospecifically in 10 steps. A five-step sequence converted the lactone to a late hemi-iminal intermediate that has resisted the methylation and spiroiminal formation that would lead to marineosin A.

Figure 1

Structure of 47b determined by X-ray crystallography. The tether is disordered with two positions for atom C10; only the major component (92.2%) is shown.

SCHEME 1

Structures and Biosynthesis of Marineosins A and B

SCHEME 2

Retrosynthesis of Marineosins A and B

SCHEME 3

Synthesis of Methoxy Iminal 16

SCHEME 4

Preparation of Spiroiminals 18–21.

SCHEME 5

Deprotection of 18c–21c

SCHEME 6

Biomimetic Synthesis of 18a–21a

SCHEME 7

Preparation of Vinyl Ketone 33

SCHEME 8

Preparation of Marineosin A Model 36

SCHEME 9

Synthesis of Macrocyclic Fused Lactone 47b

SCHEME 10

Elaboration of 47b to Hemi-iminal 52b