Revised structure of bryostatin 3 and isolation of the bryostatin 3 26-ketone from Bugula neritina

Abstract

Bryostatin 3 and the corresponding 26-ketone 5, which represents a new bryostatin, were isolated from the marine bryozoan Bugula neritina (Bugulidae). Spectmecopic data from 2D NMR studies indicate that the structure of bryostatin 3 (3) has to be revised to structure 4. Bryostatin 3 showed [sH]phorbol dibutyrate receptor displacement activity similar to that of bryostatin 1, whereas the corresponding 26-ketone 5 was significantly less active.

Biosynthesis of polyketides by trans-AT polyketide synthases

“…[203][204][205][206][207][208][209][210][211][212][213][214][215][216] Several of the initially published structures were later revised (bryostatins 3, 4, 5 and 10), 211,217 which still leads to some confusion in the literature. In addition, mass spectrometric evidence exists that bryostatins are also present in other, unrelated marine organisms.…”

“…330 Gr€ afe et al found that 199 passively conveys protons and other monovalent cations through membranes, which could explain the antibacterial and cytotoxic effects. 331 In addition to 199 and 207, several further congeners were described (200)(201)(202)(203)(204)(205)(206)(208)(209)(210)(211)(212)(213)(214)(215)(216)(217). [332][333][334][335][336][337][338] Noteworthy is the occurrence of the structurally related clathrynamides 212-217 in the marine sponges Clathria sp.…”

New Approaches to the Total Synthesis of the Bryostatin Antitumor Macrolides

“…The bryostatin antitumor macrolides [1] continue to capture the imagination and attention of chemists and life scientists alike, not only for their novel biological properties, but also for the significant challenges and opportunities they provide for doing high-level organic synthesis. In this Focus Review, we highlight some of the more significant developments that have taken place in the bryostatin total synthesis field over the period [2001][2002][2003][2004][2005][2006][2007][2008][2009], since work prior to 2001 has already been reviewed by us, [2] as well as in several even earlier review articles by Wills, [3] Wender, [4] Pettit, [5] and Paterson.…”

“…In this Focus Review, we highlight some of the more significant developments that have taken place in the bryostatin total synthesis field over the period [2001][2002][2003][2004][2005][2006][2007][2008][2009], since work prior to 2001 has already been reviewed by us, [2] as well as in several even earlier review articles by Wills, [3] Wender, [4] Pettit, [5] and Paterson. [6] Originally discovered in extracts of the marine organism Bugula neritina by George Pettit and co-workers in the late 1960s, [1] the bryostatin antitumor macrolides have now expanded to become a family of some twenty members. [1] The first bryostatin to succumb to structure elucidation was bryostatin 1, back in 1982.…”

“…[6] Originally discovered in extracts of the marine organism Bugula neritina by George Pettit and co-workers in the late 1960s, [1] the bryostatin antitumor macrolides have now expanded to become a family of some twenty members. [1] The first bryostatin to succumb to structure elucidation was bryostatin 1, back in 1982. [1a] Massive effort went into successfully establishing its molecular architecture, mainly because preliminary biological screening had revealed it to be a powerful antitumor agent in vitro; behavior that was later confirmed in vivo in a number of established murine tumor models.…”