Total syntheses of wentilactones A and B, and related norditerpene dilactones

Abstract

Wentilactone A and B, two representative tetranorditerpenoid dilactones with promising antitumor activities, are synthesized for the first time. The synthesis employs 3beta-hydroxydilactone 6 as a common precursor, which is derived...

Collective Synthesis and Cytotoxicities of Wentilactone Type Norditerpenoid Dilactones

“…Very recently, we developed an effective approach to the total synthesis of norditerpenoid dilactones bearing modifications on the A‐ring, including WA (3β‐hydroxy‐1,2‐β‐epoxide, 2 ), WB (2β‐ol, 3 ), asperolide B (2,3‐β‐epoxide, 4 ), and the unnamed natural congener (3β‐hydroxy‐1,2‐ene, 5 ), by employing 3β‐hydroxydilactone 1 as a common precursor (Figure 2). Conversion of the A‐ring‐functionalized to nonfunctionalized norditerpenoid dilactone, such as CJ‐14445 ( 6 ), was also proved feasible [31] . In the synthetic route toward wentilactone A/B, [31] we collected several derivatives, such as 2‐ketone 7 and hemiacetal 8 .…”

“…Treatment of alkene 9 at room temperature with a solution of m ‐CPBA in CHCl 3 provided exclusively 2,3‐α‐epoxy 10 in 80% yield. It is noteworthy that the 2,3‐β‐epoxide ( 4 ) was obtained through NBS‐mediated halohydrin formation and subsequent epoxide formation under the action of NaOMe [31] . Alternatively, 3β‐ol 1 was successfully converted to ▵ 1,2 ‐enone 11 by IBX‐mediated dehydrogenation [32] .…”

“…Starting from 3β‐acetate 15 , [31] which was derived from 3β‐ol 1 , we explored modification on the C‐ring (Scheme 2). Allylic oxidation of 15 with selenium dioxide afforded C14‐hemiacetal 16 , which was in equilibrium as epimers.…”

“…Conversion of the A-ring-functionalized to nonfunctionalized norditerpenoid dilactone, such as CJ-14445 (6), was also proved feasible. [31] In the synthetic route toward wentilactone A/B, [31] we collected several derivatives, such as 2-ketone 7 and hemiacetal 8. Here, we report the preparation of additional derivatives with modifica- Subjection of 3β-hydroxydilactone 1 to elimination in the presence of POCl 3 led to Δ 2,3 -derivative 9 in 90% yield (Scheme 1).…”

“…It is noteworthy that the 2,3-β-epoxide (4) was obtained through NBS-mediated halohydrin formation and subsequent epoxide formation under the action of NaOMe. [31] Alternatively, 3β-ol 1 was successfully converted to ~1,2 -enone 11 by IBX-mediated dehydrogenation. [32] Successive DIBAL-Hmediated reduction and selective PCC oxidation of the resulting hemiacetal (at C-ring) furnished Δ 2,3 -3-β-ol 5 in 80% yield; [31] whereas a (i-PrO) 3 Al-mediated reduction afforded the corresponding 3-α-ol 13, in that the α-selectivity was resulted from the coordination of aluminum cation with the oxygen of the γlactone.…”