Stereostructure Reassignment and Determination of the Absolute Configuration of Pericosine D_o by a Synthetic Approach

Abstract

A combination of chemical synthesis and NMR methods was used to reassign the structure of pericosine D(o) (8), a cytotoxic marine natural product produced by the fungus Periconia byssoides OUPS-N133 that was originally derived from the sea hare Aplysia kurodai. Chemical synthesis was used to prepare pericoisne D(o) (8) from a known chlorohydrin that was in turn derived from (-)-quinic acid. The absolute configuration of natural pericosine D(o) (8) was determined to be methyl (3R,4S,5S,6S)-6-chloro-3,4,5-trihydroxy-1-cyclohexene-1-carboxylate. HPLC analyses using a chiral-phase column indicated that pericosine D(o) (8) exists in an enantiomerically pure form in nature.

Marine natural products

“…305,306 Synthesis and NMR spectroscopic analysis were used to reassign the structure and determine the absolute conguration of pericosine D 0 , a metabolite of the sea hare-derived fungus Periconia byssoides, 307 as methyl (3R,4S,5S,6S)-6-chloro-3,4,5-trihydroxy-1-cyclohexene-1-carboxylate 403. 308 Synthesis of the proposed structure of phomopsin B, 309 a metabolite of the mangrove endophytic fungus Phomopsis sp., led to revision of the structure to that of the known dothiorelone A, previously isolated from another mangrove endophytic fungus Dothiorella sp. 310 Total synthesis of dothiorelone A/phomopsin B through a cross-metathesis with a chiral olen was then completed.…”

Synthesis of Marine-Derived Carbasugar Pericosines

“…Structural determinations of pericosines D and D o were not straightforward [64][65][66]85]. Isolation of pericosine D was reported in 1999 at the Annual Meeting of the Pharmaceutical Society of Japan, and the structure was reported as 26 [85].…”

“…But synthetic 6 had the same retention time as natural 6 in the chiral HPLC analysis. A detailed description on the chiral HPLC analysis will be given below [66]. Since the specific rotation of synthesized (À)-6 had the opposite sign ([a] D 25 À6.5) to the reported natural pericosine D o ([a] D þ1.9), the specific rotation of natural 6 was remeasured, giving an acceptable [a] D 25 value of À6.6, which suggested that the absolute configuration of natural pericosine D o was (3R,4S,5S,6S)-6-chloro-3,4,5-trihydroxy-1-cyclohexene-1-carboxylate (6).…”

“…This discrepancy may have resulted from mixed up samples of natural products and will be discussed in further detail later in the chapter [65,66]. The originally reported pericosine D was subsequently designated pericosine D o (6).…”

Synthesis of Natural O-Linked Carba-Disaccharides, (+)- and (−)-Pericosine E, and Their Analogues as α-Glucosidase Inhibitors

“…In the course of our continuing studies on the synthesis of bioactive marine natural products, we have studied and reported on the total syntheses of pericosines [ 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. Pericosines A–E ( 1 – 6 ) are unique carbasugar-type metabolites of the fungus Periconia byssoides OUPS-N133, which was originally isolated from the sea hare Aplysia kurodai [ 16 , 17 , 18 ]. As pericosine A ( 1 ) showed remarkable anticancer activity, several other research groups have also undertaken and reported the syntheses of pericosines [ 19 , 20 , 21 , 22 , 23 , 24 , 25 ].…”