Total synthesis of (±)-9-deoxygoniopypyrone. Application of the iodocyclofunctionalization reaction of bold α-allenic alcohol derivatives

Abstract

The synthesis of ( ±)-9-deoxygoniopypyrone (1) from the α-allenic alcohol 5 is described. Iodocyclofunctionaliztion of the N-tosyl carbamate derivative of 5 using I2 and Ag2CO3 provided, in a highly diastereoselective and regioselective fashion, the vinyl iodo syn-vicinal diol 4. Two routes were explored in order to introduce the third stereogenic centre in the molecule. Reductive deiodination of the vinyl iodide and diastereoselective epoxidation of the derived acetonide14 using mCPBA provided a mixture of epoxides 15 and 16 (2:1) in which the desired threo diastereomer predominated. Alternatively, dihydroxylation of acetonide 14 (OsO4, NMO) yielded a mixture of diols 21 and 22 (2:3) which were separated after monosilylation (TBDMSCl) of the primary alcohol. The major silyl ether erythro diastereomer 24 was converted to the desired epoxide 15 by mesylation (MsCl, Et3N) and epoxide formation (TBAF) with inversion of stereochemistry. The minor threo diastereomer 23 was also converted to the desired epoxide 15 (TBAF; ArSO2Cl; NaOMe). Epoxide opening was effected with lithium acetylide and the resulting alkyne 27 was carbonylated (MeLi, ClCO2Me) to afford the α , β-acetylenic ester 28. Semi hydrogenation over Lindlar's catalyst followed by protecting- group removal under acidic conditions provided ( ±)-8-epigoniodiol 30. Finally, conversion of 30 to ( ±)-9-deoxygoniopypyrone 1 was effected under basic conditions (DBU).Key words: ( ±)-9-deoxygoniopypyrone, α-allenic alcohol, iodocyclofunctionalization, syn-diol.

Asymmetric Total Syntheses of the trans-2-Aryl-6-alkyltetrahydropyrans Diospongin B and Parvistones D and E from a Common Precursor

“…[7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] Total synthesis of diospongin B has been reported by eight research groups including Jennings, 7 Uenishi, 8 Sabitha,9 Xian, 10 Kumaraswamy, 11 Taylor, 12 Hashimoto, 13 and Hall. 14 The synthesis of the bicyclic styryl lactone 9-deoxygoniopyrone (2a) was accomplished by Zhou, 15 Friesen, 16 Kumaraswamy, 17 Mukai, 18 Prasad, 19 Ramachandran, 20 and Vatèle, 21 uniformly using DBU-promoted oxa-Michael cyclization for the THP construction at the late/final stage of synthesis (except for Kobayashi 22 ), while surprisingly only one synthesis of 8-epi-9-deoxygoniopypyrone (3b) 23 was reported (by Vatèle) due to the inherent difficulty in stereoselective synthesis of 8-epi-goniodiol (e.g., anti-dihydroxylation of trans-alkene) for subsequent oxa-Michael cyclization. 24 Herein we describe the asymmetric total syntheses of (+)-diospongin B, (-)-parvistone D (2), and (+)-parvistone E (3) from a common precursor trans-2-aryl-6-alkyl THP.…”

Stereoselective Syntheses of (+)-Goniodiol, (−)-8-Epigoniodiol, and (+)-9-Deoxygoniopypyrone via Alkoxyallylboration and Ring-Closing Metathesis

“…Due to the broad spectrum of pharmacological properties associated with these molecules, several syntheses have been reported in the literature. , For example, Ley and co-workers have recently reported the synthesis of (+)-goniodiol via a Lewis acid-mediated diastereoselective oxygen-to-carbon rearrangement of an anomerically linked silyl enol ether 12f. Tsubuki et al have described a stereocontrolled synthesis of several styryllactones starting from 2,3- O- isopropylidene- d -glyceraldehyde employing NBS-mediated lactol formation, followed by chemoselective phenyl addition using triisopropoxyphenyltitanium,12i and Vatele and Surivet have synthesized enantiopure styryllactones starting from a common chiral precursor ethyl-4-( tert -butyldimethylsilyloxy)-2,3-isopropylidinedioxy-4-phenylbutanoate, prepared from ( R )-mandelic acid 12j…”