Guaianolides 1. perhydroazulenic lactones as intermediates for total synthesis

Devreese, A.; Demuynck, M.; Clercq, Pierre J. De; Vandewalle, M.

doi:10.1016/s0040-4020(01)91543-1

Cited by 22 publications

(1 citation statement)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Samarium(II) iodide was known to both effectively cleave α heteroatom substituents in ketone derivatives and reduce ketones, and thus it was surprising to find that these two transformations had not previously been coupled for producing 1,3-diols from epoxy ketones. Because Birch conditions, known to be capable of effecting this type of conversion, lacked the necessary chemoselectivity, the possibility of using samarium diiodide as an alternative was examined in some detail. It was eventually found that in the presence of excess reagent in 1% aqueous THF at 20 °C for 0.5 h, epoxy ketone 52b* suffered clean, chemoselective double reduction to generate a unique diol ( 53* ) in 83% yield.…”

Section: Resultsmentioning

confidence: 99%

First Comprehensive Bakkane Approach: Stereoselective and Efficient Dichloroketene-Based Total Syntheses of (±)- and (−)-9-Acetoxyfukinanolide, (±)- and (+)-Bakkenolide A, (−)-Bakkenolides III, B, C, H, L, V, and X, (±)- and (−)-Homogynolide A, (±)-Homogynolide B, and (±)-Palmosalide C

et al. 2002

View full text Add to dashboard Cite

Cycloaddition of dichloroketene with dimethylcyclohexenes has been used as the key reaction in an efficient, general approach to the bakkanes. New methods and methodologies that have been developed in this work include spiro beta-methylene-gamma-butyrolactonizations, a vicinal dicarboxylation, an angelic ester preparation, a transesterification, an epoxy ketone double reduction, and a retro aldol-aldol approach to low-energy aldol isomers.

show abstract

Section: Resultsmentioning

confidence: 99%

First Comprehensive Bakkane Approach: Stereoselective and Efficient Dichloroketene-Based Total Syntheses of (±)- and (−)-9-Acetoxyfukinanolide, (±)- and (+)-Bakkenolide A, (−)-Bakkenolides III, B, C, H, L, V, and X, (±)- and (−)-Homogynolide A, (±)-Homogynolide B, and (±)-Palmosalide C

et al. 2002

View full text Add to dashboard Cite

show abstract

The First Entry to Complex Bakkanes: A Highly Effective Retroaldol–Aldol-Based Approach to (−)-Bakkenolides III, B, C, and H

et al. 2000

View full text Add to dashboard Cite

Dedicated to Prof. Jean Lhomme on the occasion of his retirementSince the first members were isolated and elucidated in the late 1960s, the bakkanes have rapidly increased in number, particularly recently, so as to count now approximately 50. [1] These hydrindane sesquiterpenes of both terrestrial and marine origin, characterized by their novel spiro g-butyrolactone function and significant biological effects, [1m,n, 2] have become popular synthetic targets. To date bakkenolide A, homogynolides A and B, palmosalide C, and 9-acetoxyfukinanolide have been prepared, most more than once. [3] The nonfunctionalized and monofunctionalized bakkenolides, however, are each oxygenated singly and taken together comprise only a relatively minor number of the known bakkanes. Much more representative (ca. 80 %) of this class are the densely functionalized and stereochemically challenging C1,C9-dioxygenated bakkenolides (I, R, R 1 H, acyl). These compounds, which have significant inhibitory activity toward Hep G2, Hep G2,2,15, and P-388 tumor cell lines, [1n] as well as PAF, arachidonic acid, and collagen-induced platelet aggregation, [1m] have been isolated from Petasites japonicus Maxim. and Petasites formosanus Kitamura (Compositae). [1b±f, m, n] Herein we illustrate the first entry to this large group of bakkanes through the preparation of the representative natural bakkenolides III, B, C, and H (1 ± 4). We note in advance that this highly stereocontrolled and efficient approach allows potentially total access to the group.With its six stereocenters in the proper configurations and two hydroxyl groups which could be, in principle, easily differentiated, diol 1 (bakkenolide III) appeared to be the ideal late intermediate for accessing the entire range of known C1,C9-difunctionalized bakkenolides (Scheme 1). It seemed this diol might be secured from epoxy ketone II through chemoselective reduction, followed by stereochemical adjustments.Scheme 1. Retrosynthesis of bakkenolide III (1). [4] revealed diol 1 to have the lowest global minimum energy of the four C7,C9 diastereomers, thus it could possibly be reached through a retroaldol ± aldol equilibration. Epoxy ketone II, in turn, was viewed as arising from keto lactone 5, an intermediate previously prepared in our laboratory from 1,6-dimethylcyclohexene. [3n, 5] Keto lactone 5 was synthesized stereoselectively from enantiopure 1,6-dimethylcyclohexene (6) [3d] in five steps and 27 % overall yield [6] in a manner similar to that used earlier. It was found, however, that ring expansion could be improved by using boron trifluoride as the catalyst and that neutral conditions benefitted the transesterification [7] (Scheme 2). Scheme 2. Synthesis of keto lactone 5. a) Ref. [3d, n]; b) Zn, CH 3 CO 2 H, 70 8C, 1 h (63 %, 2 steps); c) N 2 CHCO 2 C 2 H 5 , BF 3´O (C 2 H 5 ) 2 , (C 2 H 5 ) 2 O, 0 8C, 12 h (72 %); d) HCCCH 2 OH, C 6 H 5 CH 3 , reflux, 24 h (87 %); e) Mn(O 2 CCH 3 ) 3 , C 2 H 5 OH, 20 8C, 2.5 h (68 %). Molecular mechanics calculationsOf the numerous procedures exam...

show abstract

The First Entry to Complex Bakkanes: A Highly Effective Retroaldol–Aldol-Based Approach to (−)-Bakkenolides III, B, C, and H

Hamelin

Wang

Deprés

et al. 2000

Angew. Chem. Int. Ed.

View full text Add to dashboard Cite

show abstract

Guaianolides 1. perhydroazulenic lactones as intermediates for total synthesis

Cited by 22 publications

References 29 publications

First Comprehensive Bakkane Approach: Stereoselective and Efficient Dichloroketene-Based Total Syntheses of (±)- and (−)-9-Acetoxyfukinanolide, (±)- and (+)-Bakkenolide A, (−)-Bakkenolides III, B, C, H, L, V, and X, (±)- and (−)-Homogynolide A, (±)-Homogynolide B, and (±)-Palmosalide C

First Comprehensive Bakkane Approach: Stereoselective and Efficient Dichloroketene-Based Total Syntheses of (±)- and (−)-9-Acetoxyfukinanolide, (±)- and (+)-Bakkenolide A, (−)-Bakkenolides III, B, C, H, L, V, and X, (±)- and (−)-Homogynolide A, (±)-Homogynolide B, and (±)-Palmosalide C

The First Entry to Complex Bakkanes: A Highly Effective Retroaldol–Aldol-Based Approach to (−)-Bakkenolides III, B, C, and H

The First Entry to Complex Bakkanes: A Highly Effective Retroaldol–Aldol-Based Approach to (−)-Bakkenolides III, B, C, and H

Contact Info

Product

Resources

About