Recent synthetic approaches to 6,15-iminoisoquino[3,2-b]3-benzazocine compounds.
Saframycins, safracins, renieramycins, cribrostatins, and esteinascidins are 6,15-iminoisoquino[3,2-b]3-benzazocine compounds that constitute the largest subgroup among the antitumor antibiotics belonging to the tetrahydroisoquinoline family. Their structural complexity has led to widespread synthetic attention to obtain them in both racemic and enantiopure forms. Publication in 1996 of the first total synthesis of ecteinascidin 743 by Corey's group was an important milestone, but the development of preparative protocols for these structures has continued, offering new possibilities to exploit the biological activity of the above-mentioned natural products and their analogues. This minireview is intended to update this progress following a methodological rather than a chronological organization. Besides of a brief description of the different strategies evolved from retrosynthetic analyses, which have been organized according to the order of bonding events that will link the precursors, semisynthetic approaches and a brief account of the total syntheses of ecteinascidin 743, have been analyzed.
Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad Complutense, Pza. Ramón y Cajal s/n 28040-Madrid, Spain. avendano@farm.ucm.es
Carmen
C
Avendaño
Elena
E
de la Cuesta
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001392:Azocines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004149:Dioxoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D013237:Stereoisomerism; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000077606:Trabectedin
D000970:Antineoplastic Agents; D001392:Azocines; D004149:Dioxoles; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin