Jean-Michel Vatèle

Total synthesis of antitumor Goniothalamus styryllactones

Abstract Synthesis of eight enantiopure styryllactones has been achieved from a common precursor: ethyl (2S, 3S, 4R)-4-(t-butyldimethylsilyloxy)-2,3-isopropylidenedioxy-4-phenylbutanoate16, prepared in five steps and 65 % yield from (R)-mandelic acid. Key elements for the synthesis of goniofufurone 3, goniopypyrone 4, goniobutenolides A and B (5, 6) and 7-epi-goniofufurone 7 were the introduction of the Z-acrylate moiety by a Julia coupling between 16 or its epimer in benzylic position and methyl 3-phenylsulfonyl orthopropionate 11 followed by a highly diastereoselective reduction of the resulting β-keto sulfone which sets up the last of the four contiguous asymmetric center. In the case of styryllactones 4 and 7, prior to the Julia coupling, the benzyl sterocenter of 16 was efficiently inverted by a Mitsunobu reaction. Goniodiol 1 and 9-deoxygoniopypyrone 2 were synthesized via an efficient coupling between the primary triflate derived from the common intermediate 16 or its epimer and Ghosezs sulfone 11 followed by lactonization and PhSO2H elimination. Goniodiol 1 has been efficiently converted to another styryllactone: isogoniothalamin epoxide 41. Addition of the Ghosezs sulfone to an epoxide derived from the enantiomer of 16 allowed a short synthesis of 8-epi-9-deoxygoniopypyrone 8, thereby establishing that its structure is the following: (1R, 5R, 7S, 8S) -8-hydroxy -7-phenyl-2,6- dioxabicyclo[3.3.1] nonan-3-one.

Concise total synthesis of (+)-goniofufurone and goniobutenolides A and B

Abstract Cytotoxic styryl lactones, (+)-goniofufurone and goniobutenolides A and B have been prepared in optically and diastereomerically pure form from (R)-(−)-mandelic acid via the β-hydroxy sulfone 4 as a common intermediate.

Palladium(II)-catalyzed formation of γ-butyrolactones from 4-trimethylsilyl-3-alkyn-1-ols: Synthetic and mechanistic aspects

Abstract γ-butyrolactones are obtained in good yields from 4-trimethylsilyl-3-alkyn-1-ols via Wacker-type oxidation reaction. A mechanism is proposed for this transformation: it involves two successive trans-hydroxypalladations followed by a [PdXSiMe3] syn-elimination and explains why the presence of the silyl group is essential in such a process.

Total synthesis of (+)-goniodiol

Abstract Cytotoxic styryl lactone, (+)-goniodiol 1, was prepared in enantioenriched form (ee 92%) in 15 steps from the α-(α′-alkoxyallenic) alcohol 5.

First total synthesis of (−)-8-epi-9-deoxygoniopypyrone

Abstract The structure and absolute configuration of natural 8- epi -9-deoxygoniopypyrone have been confirmed by an efficient and highly diastereoselective synthesis in 15 steps from ( S )-mandelic acid with an overall yield of 43%.

Enantioselective synthesis of (+)-goniodiol and of its naturally occurring acetylated analogs

Abstract A novel route to enantioenriched (+)-goniodiol and its natural acetylated derivatives, potent cytotoxic compounds, is described. The main features of this synthesis are transfer of the asymmetric information of the scalemic allenic alcohol 5 to the α- and β- carbons through highly diastereoselective reactions and introduction of the α,β-unsaturated lactone moiety by the Ghosez methodology.

Rearrangement of α-hydroxy imines to α-amino ketones: Mechanistic aspects and synthetic applications

Abstract In refluxing diglyme, rearrangement of α-hydroxy imines bearing diversely substituted allyl groups or a 3-trimethylsilylpropargyl group on the α-carbon to the nitrogen afforded in good yields α-amino ketones. Migration of allyl or 3-trimethylsilylallyl groups occured without allylic transposition in contrast to the 1-methylallyl group. In the 3 cases studied, the rearrangement of enantioenriched α-hydroxy imines took place with complete 1,2-chirality transfer. The rearrangement was applied to the preparation of (+)-1-benzyl-1-azaspiro[5.5]undecan-7-one, a precursor in the synthesis of (−)-perhydrohistrionicotoxin.

REACTION OF THE LITHIO-DERIVATIVE OF METHOXY ALLENE WITH SAMP-HYDRAZONES :ACCESS TO ENANTIOPURE 3-PYRROLINES

Abstract α-Lithio methoxy allene reacts with SAMP-hydrazones to give α-allenyl hydrazines 5 or 3-methoxy-3-pyrrolines 6 depending on the nature of the solvent. Both compounds have been obtained with d.e. ≥ 99 %. Hydrogenolysis of the Nue5f8N bond of 6 affords the pyrroline 7 in enantiopure form.

A short and efficient total synthesis of the cytotoxic (+)-goniodiol and (+)-9-deoxygoniopypyrone

(+)-Goniodiol 7 and (+)-9-deoxygoniopypyrone 8, belonging to the group of styryllactones, have been synthesized in five steps and 75% yield respectively from C4-esters 1a and 1b. The key step of these syntheses is a triflate-sulfone coupling which allowed a rapid construction of the backbone of the title compounds as well as the efficient installation of a masked Z-acrylate moiety.

EASY ACCESS TO AN ENANTIOPURE PRECURSOR OF (+)-GONIODIOL

Abstract Asymmetric synthesis of the epoxide 2 has been achieved from ( R )-mandelic acid 3 via highly diastereoselective Wittig reaction and erythro -selective OsO 4 catalyzed cis -hydroxylation as key steps.