Synthesis of the spiroacetal-containing anti-Helicobacter pylori agents CJ-12,954 and CJ-13,014

Abstract

The first synthesis of the spiroacetal-containing anti-Helicobacter pylori agents ent-CJ-12,954 and ent-CJ-13,014 is reported based on the union of a heterocycle-activated spiroacetal-containing sulfone fragment with a phthalide-containing aldehyde fragment; comparison of the 1H and 13C NMR data, optical rotations and HPLC retention times of the synthetic compounds (3S,2"S,5"S,7"S)-(1a) and (3S,2"S,5"R,7"S)-(2a) and the (3R)-diastereomers (3R,2"S,5"S,7"S)-(1b) and (3R,2"S,5"R,7"S)- (2b) with the naturally occurring compounds established that the synthetic isomers (1a) and (2a) were in fact enantiomeric to the natural products CJ-12,954 and CJ-13,014.

Enantioselective Iridium‐Catalyzed Phthalide Formation through Internal Redox Allylation of Phthalaldehydes

“…[16] Underscoring the utility of this method in target oriented synthesis, the preparation of 3t constitutes a formal synthesis of two different phthalide natural products: ent -spirolaxine methyl ether [17] and CJ-12,954 (Figure 2). [18] Both compounds have been shown to exhibit antibiotic activity against the Gram-negative bacteria Helicobacter pylori . [19] …”

“…[16] Underscoring the utility of this method in target-oriented synthesis,t he preparation of 3t constitutes af ormal synthesis of two different phthalide natural products: ent-spirolaxine methyl ether [17] and CJ-12,954 ( Figure 2). [18] Both compounds have been shown to exhibit antibiotic activity against the Gramnegative bacterium Helicobacter pylori. [19] In summary,wereport an enantioselective hydrogen autotransfer [20] reaction that converts o-phthalaldehydes into phthalides.I nt his processes,a symmetric aldehyde allylation triggers formation of an iridium lactolate,w hich upon b-hydride elimination delivers the phthalide.T hus,r eductive carbonyl addition is balanced by oxidative esterification to achieve an overall redox-neutral process.B eyond the parent enantioselective allylation, diverse substituted allyl donors were found to participate in this process.A dditionally,a s illustrated by the formation of phthalide 3t,t he synergistic steric and electronic influence of substituents of the ophthalaldehydes enables site-selective internal redox allylation.…”

Gold-catalyzed C–O bond forming reactions for the synthesis of six-membered O-heterocycles

“…Various biomedically important non-natural and natural systems possess spiroketals [145][146][147][148]. Most common method for the synthesis of spiroketals is the cyclocondensation of ketone diols among other developed methods [149,150] (Scheme 20). One-pot cycloisomerization on alkynediols with Au catalyst built complex ketal systems and offered many advantages.…”

Enantioselective Iridium‐Catalyzed Phthalide Formation through Internal Redox Allylation of Phthalaldehydes

“…The assignment of absolute stereochemistry for adducts 3 a – 3 t was made in analogy to phthalide 3 l , which was determined by single‐crystal X‐ray diffraction, and phthalide 3 t , which was evaluated by comparison of its optical rotation to that of an authentic sample . Underscoring the utility of this method in target‐oriented synthesis, the preparation of 3 t constitutes a formal synthesis of two different phthalide natural products: ent ‐spirolaxine methyl ether and CJ‐12,954 (Figure ) . Both compounds have been shown to exhibit antibiotic activity against the Gram‐negative bacterium Helicobacter pylori…”