Abstract
Halimedatrial, a structurally unique marine diterpene, was reported as the chemical defence adaptation in the calcareous reef-building algae Halimeda (Udoteaceae)^1. This diterpene shows potent antimicrobial activities toward a variety of marine microorganisms and also a highly inhibitory effect on the growth of a marine bacterium and a gray fungus. The structure of halimedatrial has been elucidated by NMR analysis and chemical reactions, except the absolute configuration. Herein, we wish to describe the total synthesis of 1, (+)-halimedatrial, by an enantiospecific manner starting from (S)-4-hydroxy-2-cyclopentenone. This synthesis involves stereoselective formation of the cyclopropane ring system and construction of the diformylcyclopentene moiety as crucial steps. Formation of the cyclopropane ring system was achieved by the following reactions: i) stereoselective 1,3-dipolar addition reaction of 15, prepared from (S)-4-hydroxy-2-cyclopentenone (3) via 4,5 and 11, with diazomethane to give 16, and ii) photosensitized degradation of the pyrazoline moiety to give cyclopropane derivative 17 as a major product. Lactone 17 was then converted into 24 by elongation of the side chain in 17. Construction of the diformylcyclopentene moiety was successfully carried out by stereoselective photocycloaddition of 24 with vinylene carbonate followed by oxidative cleavage of the resulting cyclobutane ring system to give (+)-halimedatrial (1). The NMR spectrum of 1 was identical with that for natural halimedatrial, though the optical rotation of 1 observed as [α]D^<25> +73.9°(c=0.28, CHCl_3) was contrary to that of the natural one, [α]D^<25> -59°(c=0.9, CHCl3). The synthesis of the antipodal (+)-halimedatrial (1) established the absolute structure of natural halimedatrial as shown in 2.
