Synthesis of C17-OH-north unit of ritterazine G via “Red-Ox” modifications of hecogenin acetate

The C17-OH-north unit of ritterazine G was prepared in 13 steps from hecogenin acetate. This synthesis features a highly efficient and stereoselective introduction of the C17-OH via E-ring cleavage/F-ring formation, D-ring oxidation, and F-ring cleavage/E-ring formation.

[1]  S. T. Phillips,et al.  Syntheses of the eastern halves of ritterazines B, F, G, and H, leading to reassignment of the 5,5-spiroketal stereochemistry of ritterazines B and F. , 2007, Journal of the American Chemical Society.

[2]  M. Boyd,et al.  Isolation and structure of cephalostatins 10 and 11. , 1994, Journal of natural products.

[3]  S. Matsunaga,et al.  Isolation of 13 New Ritterazines from the Tunicate Ritterella tokioka and Chemical Transformation of Ritterazine B(1). , 1997, The Journal of organic chemistry.

[4]  C. Blaha,et al.  OSBP Is a Cholesterol-Regulated Scaffolding Protein in Control of ERK 1 / 2 Activation , 2022 .

[5]  M. Boyd,et al.  Antineoplastic agents. 398. Isolation and structure elucidation of cephalostatins 18 and 19. , 1998, Journal of natural products.

[6]  Yoshiki Tanaka,et al.  Enantioselective synthesis of (+)-cephalostatin 1. , 2010, Journal of the American Chemical Society.

[7]  P. Fuchs,et al.  Synthesis and pharmacological evaluation of nonacyclic and trisdecacyclic pyrazines related to cephalostatin , 1992 .

[8]  P. Fuchs,et al.  A biomimetically inspired, efficient synthesis of the South 7 hemisphere of cephalostatin 7. , 2005, Journal of the American Chemical Society.

[9]  M. Boyd,et al.  Cephalostatin Synthesis. Part 11. Interphylal Product Splicing: The First Total Syntheses of Cephalostatin 1, the North Hemisphere of Ritterazine G, and the Highly Active Hybrid Analogue, Ritterostatin GN1N. , 1998 .

[10]  Zhihua Peng,et al.  [3 + 2] Annulation of Allylic Silanes in Acyclic Stereocontrol: Total Synthesis of (9S)‐Dihydroerythronolide A. , 2003 .

[11]  M. Koag,et al.  Discovery of hypoiodite-mediated aminyl radical cyclization lacking a nitrogen radical-stabilizing group: application to synthesis of an oxazaspiroketal-containing cephalostatin analog. , 2011, Organic letters.

[12]  Z. Estrov,et al.  OSW-1: a natural compound with potent anticancer activity and a novel mechanism of action. , 2005, Journal of the National Cancer Institute.

[13]  P. Fuchs,et al.  The first total synthesis of (corrected) ritterazine M. , 2002, Organic letters.

[14]  P. Fuchs,et al.  Redox refunctionalization of steroid spiroketals. Structure correction of ritterazine M. , 2002, Organic Letters.

[15]  P. Fuchs,et al.  An efficient synthesis of the C-23 deoxy, 17 alpha-hydroxy South 1 hemisphere and its cephalostatin 1 analog. , 2003, Organic letters.

[16]  P. Fuchs,et al.  Dyotropic rearrangement facilitated proximal functionalization and oxidative removal of angular methyl groups: efficient syntheses of 23'-deoxy cephalostatin 1 analogues. , 2002, Journal of the American Chemical Society.

[17]  John A. Tallarico,et al.  Natural products reveal cancer cell dependence on oxysterol-binding proteins. , 2011, Nature chemical biology.

[18]  T. Prangé,et al.  A convenient synthesis of C-22 and C-25 stereoisomers of cephalostatin north 1 side chain from spirostan sapogenins. , 2002, Organic letters.

[19]  B. Moser,et al.  The cephalostatins. 22. synthesis of bis-steroidal pyrazine pyrones (1). , 2012, Journal of natural products.

[20]  A. Vollmar,et al.  The cephalostatin way of apoptosis. , 2008, Journal of natural products.

[21]  Yong Shi,et al.  A practical synthesis of cephalostatin 1. , 2011, Chemistry, an Asian journal.

[22]  Ping-yuan Wang,et al.  OSBP Is a Cholesterol-Regulated Scaffolding Protein in Control of ERK1/2 Activation , 2005, Science.

[23]  Z. Jin,et al.  A new strategy for the stereoselective introduction of steroid side chain via alpha-alkoxy vinyl cuprates: total synthesis of a highly potent antitumor natural product OSW-1. , 2001, Journal of the American Chemical Society.

[24]  K. Woerpel,et al.  [3 + 2] Annulation of allylic silanes in acyclic stereocontrol: total synthesis of (9S)-dihydroerythronolide A. , 2003, Journal of the American Chemical Society.

[25]  P. Fuchs,et al.  Chemistry of trisdecacyclic pyrazine antineoplastics: the cephalostatins and ritterazines. , 2009, Chemical reviews.

[26]  A. Vollmar,et al.  Cephalostatin 1 selectively triggers the release of Smac/DIABLO and subsequent apoptosis that is characterized by an increased density of the mitochondrial matrix. , 2003, Cancer research.

[27]  A. Vollmar,et al.  Cephalostatin 1 Inactivates Bcl-2 by Hyperphosphorylation Independent of M-Phase Arrest and DNA Damage , 2005, Molecular Pharmacology.

[28]  B. Moser.  Review of cytotoxic cephalostatins and ritterazines: isolation and synthesis. , 2008, Journal of natural products.

[29]  D. Taber,et al.  Synthesis of Bis-18,18'-desmethyl Ritterazine N. , 2008, The Journal of organic chemistry.

[30]  P. Fuchs,et al.  Synthesis of C14,15-dihydro-C22,25-epi north unit of cephalostatin 1 via "red-ox" modifications of hecogenin acetate. , 2009, Organic Letters.

[31]  A. Vollmar,et al.  The Marine Product Cephalostatin 1 Activates an Endoplasmic Reticulum Stress-specific and Apoptosome-independent Apoptotic Signaling Pathway* , 2006, Journal of Biological Chemistry.

[32]  P. Fuchs,et al.  Synthesis of the South Unit of Cephalostatin. 7. Total Syntheses of (+)-Cephalostatin 7, (+)-Cephalostatin 12, and (+)-Ritterazine K1 , 1999 .

[33]  C. Guo,et al.  On the relationship of OSW-1 to the cephalostatins. , 1999, Bioorganic & medicinal chemistry letters.

[34]  V. Bankaitis,et al.  The oxysterol-binding protein superfamily: new concepts and old proteins. , 2012, Biochemical Society transactions.