First Total Synthesis of Antitumor Natural Product (+)‐ and (‐)‐Pericosine A (I): Determination of Absolute Stereo Structure.

Abstract

Carbohydrates U 0500First Total Synthesis of Antitumor Natural Product (+)-and (-)-Pericosine A (I): Determination of Absolute Stereo Structure. -(USAMI*, Y.; TAKAOKA, I.; ICHIKAWA, H.; HORIBE, Y.; TOMIYAMA, S.; OHTSUKA, M.; IMANISHI, Y.; ARIMOTO, M.; J. Org. Chem. 72 (2007) 16, 6127-6134; Osaka Univ. Pharm. Sci., Takatsuki, Osaka 569, Japan; Eng.) -Mischke 52-191

Enantiomeric composition of natural pericosine A derived from Periconia byssoides and α‐glycosidase inhibitory activity of (−)‐enantiomer

“…Transformation from 7 into pericosine A ( 1 ) with aqueous NaCl was also indicated in literature 9 . In view of the various biological activities of pericosine A ( 1 ) involving significant cytotoxicity against P388, inhibition against human topoisomerase II, and proteinkinase epidermal growth factor receptor, pericosines have gained attention as synthetic targets 10–19 . Pericosines have gained further attention owing to natural pericosines B ( 2 ), C ( 3 ), and E ( 6 ) existing as enantiomeric mixtures, 7,20 confirming that a lot of natural products do in fact occur as enantiomeric mixtures 21–23 .…”

“…(−)‐Pericosine A ( 1 ) 10 was prepared using the same method as the above literature 11,18 followed by a final deprotection: to a solution of (−)‐ 9 (3.0 mg, 0.099 mmol) in MeOH (0.05 ml) was added trifluoroacetic acid (0.45 ml) at 0 °C with stirring. After stirring the reaction mixture for 2 h, the solvent was removed under reduced pressure to give a crude residue, which was separated by preparative TLC (eluent: EtOAc) to (−)‐pericosine A ( 1 ) (2.2 mg, quantitative).…”

“…9 In view of the various biological activities of pericosine A (1) involving significant cytotoxicity against P388, inhibition against human topoisomerase II, and proteinkinase epidermal growth factor receptor, pericosines have gained attention as synthetic targets. [10][11][12][13][14][15][16][17][18][19] Pericosines have gained further attention owing to natural pericosines B (2), C (3), and E (6) existing as enantiomeric mixtures, 7,20 confirming that a lot of natural products do in fact occur as enantiomeric mixtures. [21][22][23] Furthermore, to date, the enantiomeric composition of pericosine A (1) from Periconia byssoides has not been clarified, despite the disagreement of the specific rotation data between natural and synthetic pericosine A.…”

“…Furthermore, to date, the enantiomeric composition of pericosine A ( 1 ) from Periconia byssoides has not been clarified, despite the disagreement of the specific rotation data between natural and synthetic pericosine A. The specific rotation of natural pericosine A ( 1 ) was reported as [α] D 20 + 57 ( c 3.16, EtOH), 6,7 whereas those of synthetic pericosine A ( 1 ) indicated considerable differences as follows: +104 ( c 0.04, EtOH), 10 +94.3 ( c 0.26, EtOH), 12 + 100 ( c 0.94, EtOH), 13 and + 105.5 ( c 0.30, EtOH) 16 …”

Production and Synthetic Modifications of Shikimic Acid

“…371,372 The total syntheses of some of these carbasugars have been accomplished by Usami and coworkers 373 after a revision of the original structure of pericosine A 374 reported by Numata et al 372 The first total syntheses of (+)-and (−)-pericosine A have been achieved starting from either quinic or shikimic acid, respectively. 375,376 Shikimic acid was used as a starting material in the preparation of the (−)-antipode of the natural product (Scheme 146), starting from methylation of the carboxylic acid and formation of the ketal 405. Oxidation of the free hydroxyl with Dess−Martin periodinane followed by stereoselective reduction of the ketone with sodium borohydride resulted in the inversion of the C-5 stereogenic center.…”