Total synthesis of rapamycin

Abstract

Details of the total synthesis of rapamycin (1) are reported. The synthesis required the preparation of intermediates 4-9 in nonracemic form; key coupling reactions included a chromium-mediated addition of vinyl iodide 8 to aldehyde 7 and an Evans aldol reaction to couple fragments 62 and 9. Intermediates 4 and 6 were joined through an amide bond formation to afford advanced intermediate 71. Swern oxidation of the diol in 71 was

Macrotricyclic Steroid Receptors by Pd°‐Catalyzed Cross‐Coupling Reactions: Dissolution of cholesterol in aqueous solution and investigations of the principles governing selective molecular recognition of steroidal substrates

“…6.1]-paracyclophane while the A ring (108 A2 hydrophobic van dev Wads surface) protrudes with its OH group at C(3) into the solvent on the wider cavity side. Such a geometry is strongly supported by the small upfield shift of the 'H-NMR signal of Me(19) at the A-B ring junction and by the large upfield shifts of the Me(l8) resonance at the C-D ring junction and of all three Me groups (Me(21), Me(26), Me (27)) of the steroidal side chain (Fig. 8).…”

“…CI yields [26]. The use of this reaction in cyclizations, however, is limited to a few cases [27]. Gratifyingly, addition of commercially available bis(tributy1stannyl)acetylene to 1 equiv.…”

Polymers for Green C–C Couplings

“…[92][93][94][95] One beautiful example is the last step of the synthesis of rapamycin reported by Nicolaou et al, which is a double Stille coupling with bis(tributyltin)ethene. [96] The drawback of the Stille reaction is the toxicity of the organotin derivatives employed. [12,97,98] The toxicity of the members of the family SnR 3 X becomes lower as the alkyl group gets larger (i.e.…”

Zum Wirkungsbereich der chemischen Synthese: Aufbau einer Minipipeline in einem akademischen Labor

“…[2] Tatsächlich sind viele der zugelassenen Wirkstoffe entweder selbst Naturstoffe oder sie stehen in eindeutigem Zusammenhang mit einer natürlichen Stammverbindung. Beispielsweise stammten Taxol, [3] Rapamycin [4] und Vancomycin [5] zuerst aus natürlichen Quellen, dagegen wurden Cabergolin und Zocor [6] durch Strukturveränderun-gen von biologisch wirksamen Naturstoffen entwickelt (Schema 1). Manchmal kann das zentrale Pharmakophor des SMNP auf eine völlig neue Strukturanordnung transferiert werden, wie das Beispiel von Lipitor zeigt.…”