Synthesis of the Potent Anticancer Agents Ottelione A and Ottelione B in Both Racemic and Natural Optically Pure Forms

Abstract

The powerful antitumor agents ottelione A and B were synthesized in racemic form by a method that relies on selective ring closing metathesis. Optically pure natural (+)-ottelione A was then made from d-ribose, via an alpha-keto cyclopropane. A key feature of the route is that the cyclopropyl group controls the stereochemistry in the attachment of the ArCH2 unit and is then converted by the action of SmI2 into a vinyl group, so that the substituents on the resulting five-membered ring have the required trans relationship. Epimerization of an intermediate gave access by the same method to the trans ring fused isomer (-)-ottelione B.

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

“…Studies for the synthesis of ottelione A and B [58] also employed this cyclopropanation methodology using a mixture of 47a and 47b . The discussion of the latter natural products is not included in this review, as phosphonamide technology was only used for limited exploratory studies.…”

Conjugated Diene-Assisted Allylic C−H Bond Activation: Cationic Rh(I)-Catalyzed Syntheses of Polysubstituted Tetrahydropyrroles, Tetrahydrofurans, and Cyclopentanes from Ene-2-Dienes

“…Benzaldehyde (1.43 g, 12.69 mmol) was dissolved in THF (10 mL) and the solution was cooled to 0 °C. Magnesium chloride S14 [9] (0.27 M in 50 mL THF, 13.5 mmol) was added dropwise to the above cooled solution. After addition, the reaction mixture was stirred at 0 °C for 10 min, and then saturated aqueous NH 4 Cl was added to quench the reaction.…”

Abnormal Behaviour of Allenylsulfones under Lu’s Reaction Conditions: Synthesis of Enantiopure Polyfunctionalised Cyclopentenes

“…In contrast, compound 8 a was cleanly transformed into 17 a in 66 % yield by treat- The compounds shown in Schemes 11-13 can be considered as synthons of optically pure, masked a-formyl cyclopentene-and cyclopentanecarboxylic acids. [32,33] To illustrate this feature, we have transformed 16 a-exo into highly functionalised cyclopentane 22, which contains four contiguous stereocentres (Scheme 14). We followed a mild, inexpensive and efficient one-pot protocol, previously reported by us, for the synthesis of acetals of 4-oxo-but-2-enoates from 5-alkoxyfuran-2(5H)-ones.…”