Shikimate-derived metabolites revised structure and total synthesis of pipoxide

Organocatalytic Asymmetric 1,6‐Addition Reactions

“…The proposed mechanism for epoxidation would involve singlet oxygen instead of reagents such as m CPBA. During the same year, the group reported a biomimetic synthesis of senepoxide ( 30 ) based on this line of thought11 (Scheme ), closely followed by a corresponding synthesis for pipoxide ( 32 ) 12…”

Naturally occurring cyclohexene oxides

“…Later work on other Uvaria plants has yielded several more such metabolites, viz: zeylenol (28) and epizeylenol (29) from the roots of U. zeylanica-27,33,34 ferrudiol (30) from the leaves of U. ferruginea,35 and metabolites of tingtanoxide and /3-senepoxide and the alcohols 31-33, from the roots of U. ferruginea.3e Although the identification of 28-30 rested mostly on NMR techniques, chemical correlations, on the other hand, played a major role in the determination of the stereochemical structures of 31-33. Thus it was shown that the diol 31 can be formed from acid hydrolysis of natural tingtanoxide (25), while the diol 32 can be obtained from the reaction of /3-senepoxide (24) with sulfuric acid. Despite the fact that the diol 32 was not a known natural product prior to its isolation from U. ferruginea, it had been synthesized by Holland's group3 by a simple chemical transformation of its precursor.…”

“…It was not until 1982 that further investigation of plants in the Uvaria genus finally provided convincing evidence for the Cole and Bates biogenetic pathway. The first missing link diene 18c [mp 90-91 °C; [a25D -276°( c 0.145, CHC13)] was discovered in the roots of U. purpurea,29 whereas the dienes 22 and 23 together with their oxidized products senepoxide 2,30 ß-senepoxide (24), and tingtanoxide (25) were isolated from the roots of U. ferruginea in the following year.31 It should be noted that 24 is, in fact, the epoxide stereoisomer of the well-known senepoxide 2, here arbitrarily assigned as -senepoxide; hence 24 becomes /3-senepoxide. The absolute stereochemistry of these compounds was determined by chemical correlations with natural products of known absolute configurations as briefly outlined below.…”

“…The diene 18c was converted to pipoxide 16 by direct epoxidation (synthetic 16, [a20D +36.3°; natural, [«20D +37.9°).29 Acetylation of 18c afforded the diene 23 (synthetic 23, [»28d -285°; natural, [a]28D -2980).31 Epoxidation of the diene 22 isolated from U. ferruginea yielded a-senepoxide (2) (synthetic 2, [a]28D -185°; natural, [a]?D -197o)3,30 and /3-senepoxide (24) (synthetic 24, [a]28D +60°; natural, [a]25D +62°).31,32 A similar reaction of the natural diene 23 gave tingtanoxide (25) (synthetic 25, [a]27D -221°; natural, [a]28D -306°) and pipoxide acetate 26 ([a]28D + 9°).31,32…”

The first enantiocontrolled synthesis of naturally occurring polyoxygenated cyclohexenylmethanol dibenzoates (–)-zeylenol, (–)-uvarigranol G, (–)-tonkinenin A and (+)-pipoxide

“…The isolation has been reported 1 of five polyoxygenated cyclohexenylmethanol dibenzoates, (-)-zeylenol 2,3 1, (-)-epizeylenol 2,4 2, (-)-uvarigranol G 5 3, (-)-tonkinenin A 6 4 and (+)-pipoxide 2,7 5, from plants of the genus Uvaria which are widely distributed across Asia, Africa, and Australia and are used in Chinese traditional medicine to treat digestive disorders. Although the structures of two, 1 and 5, have been determined unambiguously on the basis of chemical correlation 8 and the racemic synthesis of the latter as well as X-ray analysis 7 of the racemate, the structures of the other three were proposed only on the basis of spectroscopic measurements. Since the diastereo-and enantio-controlled synthesis of these natural products has so far not been reported, we were interested in the construction of these natural products utilizing the chiral cyclohexanoid building block 9 7 prepared from the mesoenediol 6 by either a catalytic 10 or an enzymatic 11 asymmetric desymmetrization procedure.…”