Studies toward the total synthesis of mitrephorone A

This Ph.D. thesis describes progress toward the total syntheses of the ent-trachylobane diterpenoid mitrephorone A. Mitrephorone A was isolated from the bark of Mitrephora glabra, an Indonesian custard apple tree. The natural product possesses an interesting molecular scaffold, comprising a hexacyclic ring system with eight stereocenters, an adjacent ketone moiety and an oxetane ring. Mitrephorone A shows moderate cytotoxic activities against tumour cell lines, which makes it a potential chemotherapeutic agent. The first part of this thesis describes our efforts to develop an enantioselective and convergent synthetic route to the core structure of mitrephorone A. The elaborated route commences with the preparation of enone I via an enantioselective Diels–Alder reaction. Conversion to alkyne II is realized in a six-step sequence involving an intramolecular Diels–Alder reaction to build up the caged structure found in the natural product. Next, the two building blocks II and III are joined via a Sonogashira cross coupling. An asymmetric dearomative cyclization of V closes the last carbon ring of mitrephorone A and sets the right quaternary stereochemistry at C10. Moreover, studies to advance precursor VI to the natural product are presented. In the second part of this thesis, we present an alternative enantioselective synthesis of the complete mitrephorone A carbon skeleton. This robust synthetic sequence starts with literature-known building block VII. A Sharpless dihydroxylation and a Robinson annulation sequence gave enone VIII, which is further converted to IX by α-vinylation and a late stage intramolecular Diels–Alder reaction. The challenging final deprotection of carbonate IX afforded triol X. In summary, a versatile synthetic strategy which yields a decorated scaffold of the ent-trachylobanes under comparably mild conditions is presented

Studies toward the total synthesis of mitrephorone A

This Ph.D. thesis describes progress toward the total syntheses of the ent-trachylobane diterpenoid mitrephorone A. Mitrephorone A was isolated from the bark of Mitrephora glabra, an Indonesian custard apple tree. The natural product possesses an interesting molecular scaffold, comprising a hexacyclic ring system with eight stereocenters, an adjacent ketone moiety and an oxetane ring. Mitrephorone A shows moderate cytotoxic activities against tumour cell lines, which makes it a potential chemotherapeutic agent. The first part of this thesis describes our efforts to develop an enantioselective and convergent synthetic route to the core structure of mitrephorone A. The elaborated route commences with the preparation of enone I via an enantioselective Diels–Alder reaction. Conversion to alkyne II is realized in a six-step sequence involving an intramolecular Diels–Alder reaction to build up the caged structure found in the natural product. Next, the two building blocks II and III are joined via a Sonogashira cross coupling. An asymmetric dearomative cyclization of V closes the last carbon ring of mitrephorone A and sets the right quaternary stereochemistry at C10. Moreover, studies to advance precursor VI to the natural product are presented. In the second part of this thesis, we present an alternative enantioselective synthesis of the complete mitrephorone A carbon skeleton. This robust synthetic sequence starts with literature-known building block VII. A Sharpless dihydroxylation and a Robinson annulation sequence gave enone VIII, which is further converted to IX by α-vinylation and a late stage intramolecular Diels–Alder reaction. The challenging final deprotection of carbonate IX afforded triol X. In summary, a versatile synthetic strategy which yields a decorated scaffold of the ent-trachylobanes under comparably mild conditions is presented

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

This review describes strategies for the chemical synthesis of xenicane diterpenoids and structurally related metabolites. Selected members from the four different subclasses of the Xenia diterpenoid family, the xenicins, xeniolides, xeniaphyllanes and xeniaethers, are presented. The synthetic strategies are discussed with an emphasis on the individual key reactions for the construction of the uncommon nine-membered carbocycle which is the characteristic structural feature of these natural products. Additionally, the putative biosynthetic pathway of xenicanes is illustrated

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

This review describes strategies for the chemical synthesis of xenicane diterpenoids and structurally related metabolites. Selected members from the four different subclasses of the Xenia diterpenoid family, the xenicins, xeniolides, xeniaphyllanes and xeniaethers, are presented. The synthetic strategies are discussed with an emphasis on the individual key reactions for the construction of the uncommon nine-membered carbocycle which is the characteristic structural feature of these natural products. Additionally, the putative biosynthetic pathway of xenicanes is illustrated

Intramolecular Vinyl Quinone Diels–Alder Reactions: Asymmetric Entry to the Cordiachrome Core and Synthesis of (−)-Isoglaziovianol

A short and asymmetric entry to the core structure of the cordiachromes has been developed, allowing access to (−)-isoglaziovianol in seven steps. Our synthesis includes a Trost asymmetric allylic alkylation and a reaction cascade triggered by a vinyl quinone Diels–Alder reaction and followed by intramolecular nucleophilic interception