Co-reporter:Koji Mizuki, Kaoru Iwahashi, Naoko Murata, Mayuko Ikeda, Yutaka Nakai, Hiroki Yoneyama, Shinya Harusawa, and Yoshihide Usami
Organic Letters 2014 Volume 16(Issue 14) pp:3760-3763
Publication Date(Web):July 3, 2014
DOI:10.1021/ol501631r
The first synthesis of (−)-pericosine E (6), a metabolite of the Periconia byssoides OUPS-N133 isolated originally from the sea hare Aplysia kurodai, has been achieved. Efficient and regioselective synthetic procedures for the synthesis of key intermediates, anti- and syn-epoxides 9 and 10, were developed using an anti-epoxidation of diene 12 with TFDO and a bromohydrination of 12 with NBS in CH3CN/H2O (2:3), respectively. In addition, comparison of the specific optical rotations between synthetic 6 and natural 6 elucidated that the naturally preferred enantiomer of pericosine E had the same absolute configuration as (−)-6 synthesized from chlorohydrin (−)-8 and anti-epoxide (+)-9.
Co-reporter:Yoshihide Usami and Koji Mizuki
Journal of Natural Products 2011 Volume 74(Issue 4) pp:877-881
Publication Date(Web):March 10, 2011
DOI:10.1021/np100843j
A combination of chemical synthesis and NMR methods was used to reassign the structure of pericosine Do (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 Do (8) from a known chlorohydrin that was in turn derived from (−)-quinic acid. The absolute configuration of natural pericosine Do (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 Do (8) exists in an enantiomerically pure form in nature.
Co-reporter:Yoshihide Usami;Yusuke Okada;Takeshi Yamada
Chirality 2011 Volume 23( Issue 1E) pp:E7-E11
Publication Date(Web):
DOI:10.1002/chir.20937
Abstract
Pericosines are carbasugar-type metabolites of Periconia byssoides OUPS-N133, a fungus that was originally separated from the sea hare Aplysia kurodai. It has been reported that pericosines C and E are enantiomeric mixtures. The difference in specific rotation between natural pericosine C and the synthetic one led to the conclusion that natural pericosine C is an enantiomeric mixture. Meanwhile, the small specific rotation of natural pericosine B compared to that of the synthetic one led to the deduction that natural pericosine B might also be an enantiomeric mixture. Then, racemic pericosines B and C were synthesized, and the direct enantioseparation of these racemic carbasugars was conducted with CHIRALPAK® IA and CHIRALPAK® AY-H, which are suitable columns for racemic pericosines B and C, respectively. Using chiral HPLC, we conclude that natural pericosines B and C exist as enantiomeric mixtures. A rare example of the application of direct chiral HPLC analysis to intact sugars or carbasugars was provided. Chirality 2011. © 2011 Wiley Periodicals, Inc.
Co-reporter:Yoshihide Usami, Marie Ohsugi, Koji Mizuki, Hayato Ichikawa and Masao Arimoto
Organic Letters 2009 Volume 11(Issue 12) pp:2699-2701
Publication Date(Web):May 27, 2009
DOI:10.1021/ol9008188
An efficient synthesis of antitumor marine natural product (+)-pericosine A was achieved from (−)-quinic acid in 11.7% overall yield, which is 20 times better than our previously reported synthesis. The crucial steps of this synthesis include the regio- and stereoselective bromohydrination of an unstable diene and the ring opening of an epoxide. This synthetic route was applicable to a synthesis of (+)-pericosine C and also to a synthesis of (−)-pericosine C.
Co-reporter:Yoshihide Usami, Kentaro Suzuki, Koji Mizuki, Hayato Ichikawa and Masao Arimoto
Organic & Biomolecular Chemistry 2009 vol. 7(Issue 2) pp:315-318
Publication Date(Web):13 Nov 2008
DOI:10.1039/B813072H
The stereoselective synthesis of (−)-pericosine B, which is the antipode of the cytotoxic metabolite of the fungus Periconia byssoides OUPS-N133 separated from the sea hare, was accomplished in 9 steps in 12% total yield from (−)-quinic acid, together with the synthesis of its epimer. Every crucial step of this total synthesis, including ring opening of a β-epoxide and NaBH4reduction of an unstable β,γ-unsaturated enone, proceeded with excellent stereoselectivity.
Co-reporter:Yoshihide Usami, Koji Mizuki, Hayato Ichikawa, Masao Arimoto
Tetrahedron: Asymmetry 2008 Volume 19(Issue 12) pp:1461-1464
Publication Date(Web):30 June 2008
DOI:10.1016/j.tetasy.2008.06.008
The synthesis of two diastereomers of pericosine A from (−)-quinic acid was achieved, thus enabling the confirmation of the relative configuration and elucidation of the absolute stereochemistry of cytotoxic natural product pericosine D assigned as methyl (3R,4R,5S,6R)-6-chloro-3,4,5-trihydroxy-1-cyclohexene-1-carboxylate.Methyl (3R,4R,5S,6S)-6-chloro-3,4,5-trihydroxy-1-cyclohexene-1-carboxylateC8H11O5Cl[α]D25=-101.0 (c 0.20, EtOH)Chiral source: synthesis from (−)-quinic acidAbsolute configuration: (3R,4R,5S,6S)Methyl (3R,4R,5S,6R)-6-chloro-3,4,5-trihydroxy-1-cyclohexene-1-carboxylate, (−)-pericosine DC8H11O5Cl[α]D25=-275.4 (c 0.04, EtOH)Chiral source: synthesis from (−)-quinic acidAbsolute configuration: (3R,4R,5S,6R)
Co-reporter:Yoshihide Usami, Kentaro Suzuki, Koji Mizuki, Hayato Ichikawa and Masao Arimoto
Organic & Biomolecular Chemistry 2009 - vol. 7(Issue 2) pp:NaN318-318
Publication Date(Web):2008/11/13
DOI:10.1039/B813072H
The stereoselective synthesis of (−)-pericosine B, which is the antipode of the cytotoxic metabolite of the fungus Periconia byssoides OUPS-N133 separated from the sea hare, was accomplished in 9 steps in 12% total yield from (−)-quinic acid, together with the synthesis of its epimer. Every crucial step of this total synthesis, including ring opening of a β-epoxide and NaBH4reduction of an unstable β,γ-unsaturated enone, proceeded with excellent stereoselectivity.
