Total Synthesis of (−)-Sacidumlignans B and D

Abstract

The first total synthesis of naturally occurring sacidumlignans A (1), B (2), and D (4) was executed and the absolute configuration of 2 and 4 was determined. A diastereoselective α- methylation of a lactone was used as the key step for the control of the chiral centers of the central lignan core. An acid mediated dehydrative cyclization of an aldehyde to construct the dihydronaphthalene unit of 2 and the aromatization of the intermediate dihydronaphthalene derivative to synthesize 1 are the key reactions employed in this regard.

Recent strategies and tactics for the enantioselective total syntheses of cyclolignan natural products

“…From (+)-deoxypicropodophyllin (37), incorporation of a C8 0 phenylselenyl group produced two diastereomers that were separated via column chromatography and then each subjected to syn-elimination via the corresponding phenylselenoxides to deliver both (+)-b-apopicropodophyllin (41) and g-apopicropodophyllin (42) in 9 total steps. 31 Their synthetic strategy involved the formation of the C1-C7 bond from a benzhydryl synthon (Scheme 9) via pathway A (Fig. 3A).…”

Recent advances in the total synthesis of 2,7′-cyclolignans

“…37 This typical dihydronaphthalene cyclolignan had been synthesized by Ramana et al previously. 38 In our work, a base-promoted addition of DMA ( N , N -dimethylacetamide) to 1,1-diarylethylenes ( e.g. , 125 ) was developed to establish a C8–C8′ bond in the target.…”

Organocatalytic Enantioselective Vinylogous Pinacol Rearrangement Enabled by Chiral Ion Pairing

“…First, submitting racemic b,g-unsaturated ketone 2a to our standard reaction conditions led only to the recovery of (AE)-2a without any enantioenrichment. Chemoselective CBS reduction [22] with catalyst (S)-6 afforded syn-7 and its anti isomer in yields of 80 %and 11 %, respectively.T reatment of diastereomerically pure syn-7 with N-bromosuccinimide (NBS) [23] afforded tetrahydrofuran 8,a na nalogue of sacidumlignan D, [24] in 87 %yield. [20] Second, performing the reaction of 1g in the presence of EtOH (6.0 equiv) under otherwise identical conditions afforded ethoxylated product 4 in racemic form and 98 %y ield (Scheme 4a).…”

“…[21] Further transformations of b,g-unsaturated ketone 2a were performed to illustrate the synthetic potential of our reaction (Scheme 5). Chemoselective CBS reduction [22] with catalyst (S)-6 afforded syn-7 and its anti isomer in yields of 80 %and 11 %, respectively.T reatment of diastereomerically pure syn-7 with N-bromosuccinimide (NBS) [23] afforded tetrahydrofuran 8,a na nalogue of sacidumlignan D, [24] in 87 %yield. Hydrogenation of 2a(Pd/C,H 2 ,EtOAc) furnished saturated ketone 9 in 91 %yield.…”