Apoptolidin: Induction of Apoptosis by a Natural Product

Abstract

Apoptolidin is a natural product that selectively induces apoptosis in several cancer cell lines. Apoptosis, programmed cell death, is a biological key pathway for regulating homeostasis and morphogenesis. Apoptotic misregulations are connected with several diseases, in particular cancer. The extrinsic way to apoptosis leads through death ligands and death receptors to the activiation of the caspase cascade, which results in proteolytic degradation of the cell architecture. The intrinsic pathway transmits signals of internal cellular damage to the mitochondrion, which loses its structural integrity, and forms an apoptosome that initiates the caspase cascade. Compounds which regulate apoptosis are of high medical significance. Many natural products regulate apoptotic pathways, and apoptolidin is one of them. The known synthetic routes to apoptolidin are described and compared in this Review. Selected further natural products which regulate apoptosis are introduced briefly.

Use of sultines in the asymmetric synthesis of polypropionate antibiotics

“…Syntheses of apoptolidinone A, the aglycone of 1, were reported by the groups of Sulikowsky [143], Crimmins [144], Nicolaou [138][139][140], and Koert [141,142]. In addition, several studies on the synthesis of fragments of apoptolidinones have been reported [137,[145][146][147][148][149][150][151][152][153][154][155].…”

O-Glycosylation methods in the total synthesis of complex natural glycosides

“…Aer ring closure of 11 using the Mo-catalyzed olen metathesis, 73 the resultant cyclolactam 12 was subjected to a stereocontrolled hydrogenation. Subsequent cleavage of the acetyl and triuoroacetyl groups with hydrazine at room temperature afforded Sch 38516 (8) in 63% yield (for three steps).…”

Methods for the Chemical Synthesis of Noncoded α‐Amino Acids found in Natural Product Peptides

“…Discovery of natural products that can induce apoptosis of cancer cells has been a major research area in development of novel anticancer agents [43]. In 1998, Umezawa et al isolated hexadepsipeptides polyoxytoxins A and B from Streptomyces culture broth.…”

“…Evans and Weber used a diastereoselective aldol method of synthesizing MeBmt that provided the amino acid in high optical purity (>99% d.e.) after chromatography and recrystallization (Scheme 5.40) [43,142]. While the Evans synthesis provided MeBmt 162, efforts continue in search of a more efficient synthesis that will allow for the production of multigram quantities of MeBmt.…”