Enantioselective synthesis of (+)-brevipolide H

Abstract

The enantioselective synthesis of natural brevipolide H is reported for the first time. By way of Sharpless epoxidation of penta-1,4-dien-3-ol, both enantiomerically pure epoxides were converted to the corresponding olefins for cross metathesis. Subsequent transformations, including epoxide ring opening, esterifications, cyclopropanation, oxidation and ring-closing metathesis, provided the target molecule. This synthesis successfully addresses previous shortcomings in preparing brevipolides.

The (+)-Brevipolide H Displays Anticancer Activity against Human Castration-Resistant Prostate Cancer: The Role of Oxidative Stress and Akt/mTOR/p70S6K-Dependent Pathways in G1 Checkpoint Arrest and Apoptosis

“…Notably, the inhibition of both Bcl-2 and Bcl-xL may play a crucial role, not only in mitochondrial dysfunction, but also in supporting intracellular calcium mobilization and Akt inhibition, although interactive regulation needs further elucidation. synthesized and published previously [13]. The compound was solubilized in DMSO.…”

“…Poly(vinylidene fluoride) (PVDF) membrane was purchased form Pall Gelman Laboratory (Ann Arbor, MI, USA). The (+)-brevipolide H was totally synthesized and published previously [ 13 ]. The compound was solubilized in DMSO.…”

“…However, the anticancer mechanism of brevipolides has not been clearly identified, although several studies have reported that they display inhibitory activity on chemokine receptor CCR5 [14] and nuclear factor-κB (NF-κB) [11] using calcium mobilization and enzyme-based NF-κB assays. We successfully synthesized (+)-brevipolide H, one of the active components in brevipolides, and the bioactive examination showed potent anti-proliferative effects in CRPC cell lines [13]. The results prompted the elucidation of the anti-CRPC mechanism of (+)-brevipolide H in this study using the PC-3 cell model, a bone metastasis-derived CRPC cell line.…”

“…The utilization of natural products and their structures in the research and development of cancer drug entities continues to gain substantial attention. Brevipolides, a series of 5,6-dihydro-α-pyrone derivatives from Hyptis brevipes, have been found to exhibit anticancer activities against colon cancer, breast cancer, nasopharyngeal cancer, laryngeal cancer, and prostate cancer [11][12][13]. However, the anticancer mechanism of brevipolides has not been clearly identified, although several studies have reported that they display inhibitory activity on chemokine receptor CCR5 [14] and nuclear factor-κB (NF-κB) [11] using calcium mobilization and enzyme-based NF-κB assays.…”

Antiparasitic Metabolites from Hyptis brevipes, a Tacana Medicinal Plant

“…These were originally isolated by cytotoxicity-based assays, in particular those listed as brevipolides (A-J), share a cis--unsaturated carbonyl system as part of a -lactone attached to a hydroxylated and esterified hexyl chain, bearing a cyclopropane moiety and several stereogenic centers within their skeleton, and for which the absolute stereochemistry was assigned by spectroscopic, chemical and synthetic methods as: 6R, 1'S, 2'S, 4'S and 6'S. No other brevipolides with different stereochemistry have so far been reported, additionally from this plant, two insecticidal flavonoids and some inactive terpenoids were also described [6][7][8][9][10][11].…”