Rachid Chahboun

SYNTHESIS AND ANTITUMOR ACTIVITY OF PUUPEHEDIONE AND RELATED COMPOUNDS

Abstract The first enantiospecific synthesis of bioactive marine puupehedione ( 2 ) and related compounds from (−)-sclareol ( 11 ) is reported. The antitumor activity of these compounds was assayed and compared with that of the natural products.

Enantiospecific synthesis of (+)-puupehenone from (−)-sclareol and protocatechualdehyde

Abstract The first enantiospecific synthesis of the antitumor and cholesteryl ester transfer protein (CETP) inhibitor (+)-puupehenone (19) from (−)-sclareol (10) and protocatechualdehyde (4) is described. The key steps of the reaction sequence are the organoselenium-induced cyclization of the mixture of regioisomers 15a-b to give 16 and 17, with complete diastereoselectivity, and the simultaneous removal of benzyl and phenylselenyl groups of 16 and 17 by treating with Raney Ni.

Synthesis and antitumoral activities of marine ent-chromazonarol and related compounds

Efficient syntheses of ent-isozonarol (6a), ent-isozonarone (7a) and ent-chromazonarol (8) from (-)-sclareol (12) are described. 6a and 7a show a significative antitumoral activity.

SYNTHESIS OF WIEDENDIOL-A AND WIEDENDIOL-B FROM LABDANE DITERPENES

Abstract Two efficient enantiospecific syntheses of wiedendiol-A (1) from (−)-sclareol (7), via 11-bromo-8-drimene (11) and 8-drimen-11-al (3), are reported. The first enantiospecific synthesis of wiedendiol-B (2), via 8S,9S-driman-11-al (26), by two alternative routes starting from 7 and (+)-cis-abienol (8) is also described. 21 prepared from protocatechualdehyde (17) was used as aromatic synthon for preparing 1 and 2.

A Very Efficient Route toward the 4a-Methyltetrahydrofluorene Skeleton: Short Synthesis of (±)-Dichroanone and (±)-Taiwaniaquinone H

A very expedient and efficient new route toward taiwaniaquinoids, bearing the 4a-methyltetrahydrofluorene skeleton, is reported. Key steps are the intramolecular Friedel-Crafts alkylation of an aryldiene and the degradative oxidation of a methylenedioxy group; the latter process could also be utilized for building the 2-hydroxy-1,4-benzoquinone unit, which is frequently found in natural products. Utilizing this new methodology, (+/-)-dichroanone (7) (three steps, 77% overall yield) and (+/-)-taiwaniaquinone H (6) (four steps, 70% overall yield) have been synthesized from commercial alpha- (11a) or beta-cyclocitral (11b).

General Access to Taiwaniaquinoids Based on a Hypothetical Abietane C7–C8 Cleavage Biogenetic Pathway

A new strategy for synthesizing taiwaniaquinoids, a group of terpenoids with an unusual rearranged 5(6→7) or 6-nor-5(6→7)abeo-abietane skeleton, which exhibit promising biological activities, is reported. The procedure, based on the cleavage of the C7-C8 double bond of abietane diterpenes, is the only one yet reported for synthesizing C(20) taiwaniaquinoids bearing a carbon function on the cyclopentane B ring; it is also applicable to the synthesis of the wide variety of existing taiwaniaquinoids. Utilizing this, (-)-taiwaniaquinone A, F, G, and H, (-)-taiwaniaquinol B, and (-)-dichroanone have been synthesized from (+)-abietic acid. The versatility of this strategy allows us to propose the abietane C7-C8 cleavage as a possible biosynthetic pathway to this type of rearranged diterpenes; this proposal seems to be supported by phytochemical evidence.

Enantiospecific Synthesis of Wiedendiol-B from (−)-Sclareol and (+)-cis-Abienol

Abstract The first enantiospecific synthesis of the cholesteryl ester transfer protein (CETP) inhibitor wiedendiol-B (1) is described. The drimanic synthon was prepared from (−)-sclareol (4) and (+)-cis-abienol (13) by two alternative routes. The key steps of the reaction sequences are the chemo- and diastereoselective hydrogenation of the C8-C9 double bond of enal 6 and the stereoselective cationic hydrogenation of the hydroxyl group of 13, respectively, and the selective reduction of benzyl groups of 15.

First synthesis of achilleol A using titanium(III) chemistry

Described herein is a straightforward synthesis of the monocyclic triterpene achilleol A using as key step titanium(III) chemistry. This synthesis confirms the previously described structure based on spectroscopic methods.

Synthesis of monoterpenic analogues of puupehenone and puupehedione

Abstract Compounds 7–8 , monoterpenic analogues of the marine metabolites puupehenone ( 1 ) and puupehedione ( 2 ), were prepared from the easily available β-cyclocitral ( 10 ) and the aryllithium derived from 11 and 12. 8 showed antitumoral activity 4–10 times higher than that for the natural products. 8 showed antitumoral activity 4–10 times higher than that of natural puupehedione.

Degradation of the Side Chain of (−)‐Sclareol: A Very Short Synthesis of nor‐Ambreinolide and Ambrox

Abstract The synthesis of nor‐Ambreinolide (8) from (‐)‐sclareol (1) was carried out by treatment with KMnO4‐Ac2O and further alkaline hydrolysis. 8 was directly transformed into (‐)‐ambrox (11) by reduction with metal borohydride in the presence of Lewis acids.