A New, Highly Stereoselective Synthesis of β-Unsubstituted (Z)-γ-Alkylidenebutenolides Using Bromine as a Removable Stereocontrol Element

Abstract

Several b-unsubstituted (Z)-g-alkylidenebutenolides have been prepared in highly stereocontrolled fashion by implementing a steric directing group stratagem in the vinylogous aldol condensation of butenolides with aldehydes. Applications to the synthesis of the antitumor heptene (S)-melodorinol and a thiophenelactone from Chamaemelum nobile L. are described.

Antiproliferative compounds ofArtabotrys madagascariensisfrom the Madagascar rainforest

“…The existence of benzoyl derivatives in Annonaceous plants is not uncommon, and a brief summary of biosynthetic origins of these compounds has been published [13]. However, there have been few reports involving the isolation of such C-7 benzoyl derivatives [13][14][15], and total synthesis of these compounds by various methods has been reported [16][17][18][19][20].…”

Synthesis of revised structure of klaivanolide (acetylmelodorinol)

“…[11][12][13][17][18][19][20][21] All the spectral data was compared with published data and found to be identical. [11][12][13][17][18][19][20][21] The compounds cismelodorinol (5) and trans-melodorinol (6) were subjected to acetylation to give corresponding acetylmelodorinol 2 and its trans-isomer 7, respectively. All the spectral data of the synthetic racemic acetylmelodorinol 2 is in complete agreement with the literature reports.…”

“…Although synthesis of acetylmelodorinol was known in the literature by four different routes, [17][18][19][20][21] we wanted to synthesize the same target using a short sequence which is amenable to analogues synthesis. Our planned synthesis began with a known aldehyde 4 prepared from corresponding olefin through ozonolysis, [22][23] which was subjected to aldol condensation with 2-furanone 24 followed by exposure to triethylamine/acetic anhydride produced a mixture of E/Zisomers of 3 (~1:3 ratio).…”

Total Synthesis of the Antitumor Antibiotic Basidalin

“…Access to A was to be gained from bromobutenolide B, which would in turn derive from C with D by utilizing our stereodirected vinylogous aldol condensation (SVAC) method. 12 Previously, we had used bromine as a removable stereocontrol element for making (Z)−β−unsubstituted−γ−alkylidenebutenolides. 12 In the present instance, bromine would serve the dual purpose of The synthesis began with 2-formyl-1,3-dithiane 11 and 2-silyloxyfuran 12 (Scheme 3), each prepared in one step from commercial chemicals.…”