Total Synthesis of Violaceoid A and (−)- and (+)-Violaceoid B

Abstract

The first total synthesis of violaceoid A, a cytotoxic agent, and the asymmetric total synthesis of (−)-and (+)-violaceoid B are reported. The precursor was accessed by desymmetrization of a substituted quinol moiety, and the racemic secondary alcohol was kinetically resolved using a chiral nucleophilic catalyst. The asymmetric synthesis of (−)-and (+)-violaceoid B elucidated the absolute configuration of the naturally occurring violaceoid B. Synthetic violaceoid A inhibited the growth of human breast cancer cell lines MCF-7 and Hs 578T at concentrations of less than 100 μM, while (S)-and (R)violaceoid B were inactive.

Total Synthesis of Eutyscoparol A and Violaceoid C

“…The synthesis of aldehyde 5, as outlined in Scheme 1, began with the direct transformation of dinitrile 6 to diester 7, [7] achieving a yield of 52%. This yield is comparable to the combined yield of the hydrolysis and esterification steps in our prior work, [3] effectively eliminatiing one step in the process. Subsequently, the hydroxy groups of the ester were protected using tertbutyldiphenylsilyl (TBDPS) group, resulting in protected ether 8.…”

“…We previously reported the first total synthesis of violaceoid A and violaceoid B in 2018. [3] Recently, in 2021, Narita, Watanabe and coworkers reported the concise total synthesis of violaceoid A (1) and the first total synthesis of violaceoid C (3). [4] Followin these development, we achieved the first total synthesis of eutyscoparol A (4) and total synthesis of violaceoid C (3).…”

Total Synthesis of Eutyscoparol A and Violaceoid C

“…We previously reported the first total syntheses of violaceoid A and violaceoid B in 2018. [4] Recently, in 2021, Narita, Watanabe and co-workers reported the concise total synthesis of violaceoid A (1) and the first total synthesis of violaceoid C (3). [5] As another efficient synthesis of 1, Matsushima and coworkers reported the simple total synthesis of 1 via 4.…”

Concise Syntheses of Violaceoids A and C

“…The first total syntheses of 1 and 2 were performed by Shiina et al in 2018, and the absolute configuration of 2 was established by its synthesis. 7) They utilized 3,6-dihydroxyphthalonitrile as a starting material, and the synthetic route required a relative multistep sequence involving protection-deprotection and oxidation-reduction steps (1: 10 steps, 11% overall yield; 2: 21 steps, including several repetitive kinetic resolutions and acetonide deprotection steps and 1.3% overall yield). In this study, we observed that boronic acid played a dual role, as a protective and coupling reagent, in the Suzuki-Miyaura cross-coupling of 3-bromo-2-(hydroxymethyl)phenol, and a concise synthesis of 1 employing this strategy was described.…”