Jean-Pierre Férézou

REACTIVITY OF (E)-1-(TERT-BUTYLDIMETHYL)SILYLOXY-3,3-BIS(TRIBUTYLSTANNYL)-PROPENE : SYN SELECTIVE SE'ADDITION TO ALDEHYDES

Abstract The reactivity of ( E )-1-( tert -butyldimethyl)silyloxy-3,3-bis(tributylstannyl)propene 1 as potential 1,3 dianion equivalent has been investigated. Condensation with aldehydes 4a–h , in presence of BF 3 ·OEt 2 , afforded in high yields the mono-protected diols 5a–h exhibiting an exclusive E configuration of the vinyltin residue. Good to high syn selectivities have been measured, in agreement with an S E′ addition mechanism. Further transformation of the resulting vinyltin moiety of these diols into various functionalities has been successfully tested.

Diastereoselective synthesis of a taxane precursor

Abstract A highly diastereoselective synthesis of the taxane potential precursor 16 is achieved. An unexpected diastereoselectivity was observed upon condensation of the α-trimethylsilyloxyaldehydes 9a or 9b with the cyclohexenyllithium 10 . The single diol isomers 13A and 14A exhibiting the required 1β,2α relative configuration are obtained in good yields.

Sirodesmin PL biosynthesis in Phoma lingam tode

The biosynthesis of sirodesmin PL (1) in the fungus Phoma lingam Tode has been investigated using different labelled precursors : [1-14C]-, [1-13C]-, [1,2-13C2]-acetates, L-[U-14C]serine, L-[U-14C]tyrosine, [14C] phomamide (3) or [14C]cyclo-L-tyrosyl-L-serine (4). A scheme is proposed in agreement with the demonstration of the mevalonic origin of the tetrahydrofuranone ring, the incorporation of radioactivity from serine and tyrosine, and the easy conversion of the two cyclodipeptides (3) and (4) into sirodesmin PL (1).

Kalanchosine Dimalate, an Anti-inflammatory Salt from Kalanchoe brasiliensis

This report describes the isolation and characterization of kalanchosine dimalate (KMC), an anti-inflammatory salt from the fresh juice of the aerial parts of Kalanchoe brasiliensis. KMC comprises the new metabolite kalanchosine (1) and malic acid (2) in a 1:2 stoichiometric ratio. Kalanchosine (1), 3,6-diamino-4,5-dihydroxyoctanedioic acid, is the first naturally occurring dimeric bis(gamma-hydroxy-beta-amino acid) and is at least partially responsible for the anti-inflammatory properties of K. brasiliensis.

“Abnormal” eight-membered ring formation through SN2′ intramolecular Nozaki/Kishi reaction in a synthetic approach to a taxane precursor

Two different reactions were experimented for the construction of the eight-membered B-ring of taxane skeleton through the formation of the C9ue5f8C10 bond. A SmI 2 promoted radical reaction on seco -alkynyl aldehydes 11 cis or 11 trans failed. A Nozaki/Kishi reaction carried out on the seco -iodovinyl aldehyde 12 trans led, through an unprecedented intramolecular S N 2′ reaction, to the “abnormally” cyclised product 14 , the structure of which has been confirmed by X-ray crystallography.

Structure and biosynthesis of phomenoic acid, an antifungal compound isolated from Phoma lingam Tode

On the basis of 1H and 13C n.m.r. studies, ozonolysis, and biosyntheses from [13C]acetates and [methyl-13C]methionine, structure (1) is proposed for phomenoic acid, an antifungal compound isolated from the mycelium of the fungus Phoma lingam Tode.

Ivermectin-derived leishmanicidal compounds

In the present study a family of macrocyclic and acyclic analogues as well as seco-analogues of avermectins were prepared from commercial Ivermectin (IVM) and their antileishmanial activity assayed against axenic promastigote and intracellular amastigote forms of Leishmania amazonensis. Contrarily to the filaricidal activity, the leishmanicidal potentiality of avermectin analogues does not appear to depend on the integrity of the non-conjugated Delta(3,4)-hexahydrobenzofuran moiety. Conjugated Delta(2,3)-IVM or its corresponding conjugated secoester show higher anti-leishmania activity than the parent compound. Surprisingly, the diglycosylated northern sub-unit exhibits the same anti-amastigote potentiality as the southern hexahydrobenzofuran. As expected for compounds derived from the widely used Ivermectin antibiotic, little toxicity has been noticed for most of the novel analogues prepared.

Preparation of 3,3-bis(Tributylstannyl)propenes, Potential New 1,3-Allyl Dianions

(E)-1-(tert-Butyldimethyl)silyloxy-3,3-bis(tributylstannyl)propene 11 as well as 1-N,N-diisopropylcarbamoyloxy-3,3-bis(tributylstannyl)propene 10 have been prepared upon addition of Bu3Sn(Bu)Cu(CN)Li2 8 to diverse γ-heterosubstituted acrolein precursors, followed by addition of excess HMPA and of the required electrophile. A E/Z ratio of 95:5 was reached in the case of 11. The reaction may occur through an addition-elimination-addition sequence where the stannylated acrolein B is thought to be a common intermediate. The best results were obtained upon single conjugate addition of 8 to (E)-3-(tributylstannyl)-2-propenal 12 (78%). A two-pot synthesis of the title compound was developed from the inexpensive malonaldehyde bis(dimethyl)acetal 14.

Structure and synthesis of phomamide, a new piperazine-2,5-dione related to the sirodesmins, isolated from the culture medium of Phoma lingam Tode

Several active substances are produced by the fungus Phoma lingam Tode, among which are the previously reported sirodesmins PL (1) and (2), sulphur-containing piperazinediones. A new metabolite, phomamide, also a piperazine-2,5-dione, has now been isolated from the culture filtrate of the same fungus. On the basis of physicochemical and spectroscopical data, the structure (3) of cyclo-O-(γγ-dimethylallyl)-L-tyrosyl-L-serine has been demonstrated for this compound and confirmed through subsequent synthesis. This metabolite is assumed to be an intermediate in the biosynthesis of the sirodesmin group of antibiotics.

Easy transformations of vinyl N,N-diisopropyl carbamates into silyl enol ethers or aldehydes by addition of methyllithium

Abstract Homoaldols and 4-hydroxy silyl enol ethers have been prepared upon addition of methyllithium to 4-hydroxyvinyl N,N -diisopropyl carbamates obtained from Hoppes homoaldolisation reaction followed by addition, in presence of an excess of HMPA, of water or tert -butyldimethylsilyl chloride, respectively. In the case of silyl enol ethers, a total retention of the Z configuration of the double bond was observed. This simple procedure allows an easy preparation of γ-lactones from the homoaldol adducts.