Divergent Asymmetric Total Synthesis of Mulinane Diterpenoids

Abstract

A concise, divergent, asymmetric total syntheses of mulinane diterpenoids has been achieved. Specifically, a new strategy was developed featuring a key intramolecular Friedel-Crafts reaction to construct the chiral fused 5-6-6 tricyclic motif, followed by sequential Birch reduction, conjugate methylation, and homologation/ring-expansion reactions to furnish the desired 5-6-7 tricyclic skeleton bearing five contiguous stereocenters. With this efficient strategy, seven mulinane diterpenoids and two analogues were synthesized via late-stage functional modification or functionalization in 8.6-20 % overall yields and 11-15 steps.

Protecting-Group-Free Total Synthesis of Anticancer (±)-Melotenine A

“…Next, compound 8 was treated with NaBH 3 CN under acidic conditions to give compound 9 with almost quantitative yield (99%). Without purification by column chromatography, this compound subsequently underwent an intermolecular aza-Michael reaction with 3-butyn-2-one (10) to provide vinylogous amide 11 in an excellent yield (90%). 4a Under acidic conditions, this compound further underwent an intramolecular Michael reaction followed by isomerization to afford bridged indoloazepine 12 in 98% yield.…”

Advances in the synthesis of 1,2-dioxolanes and 1,2-dioxanes

“…Reaction of mulinic acid with a ruthenium complex gave rise to the formation of isomulinic acid (Scheme 64). 228 Another interesting example transformed 1,2-dioxenes into furans under Appel reaction conditions. Thus, diene 395 underwent first a cycloaddition with singlet oxygen to form 1,2-dioxene 396 and further reaction with PPh3 and CBr4 led to 397 in good yield.…”

Mulinane- and Azorellane-Type Diterpenoids: A Systematic Review of Their Biosynthesis, Chemistry, and Pharmacology

“…Recently, Liu et al achieved the enantioselective total synthesis of natural mulinanes and analogous from cyclopentenone ( Table 2, and Figure 4) [53]. In addition, the presence of different functional groups, which include hydroxyl, carboxyl, acetoxy, and double bond, in the mulinane skeleton has allowed the preparation of a significant number of semisynthetic derivatives using dehydration, alkylation, hydrolysis, and oxidation reactions ( Table 3, and Figure 5).…”