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DOI: 10.1055/s-2006-958967
A Practical Synthesis of the Ansa Chain of Benzenic Ansamycin Antibiotics: Total Synthesis of an Ansatrienol Derivative
Publication History
Publication Date:
10 January 2007 (online)
Abstract
A practical and stereocontrolled synthetic approach towards the ansa chain of the benzenic ansamycins (mycotrienins) is described, which can be scaled up to multigram quantities. Key features of the synthesis are the formation of the Z-configured trisubstituted double bond by a one-pot esterification of allyl(diisopropoxy)borane and ring-closing metathesis, formation of the β-keto ester via ethyl diazoacetate addition to an aldehyde, and use of the Duthaler-Hafner acetate aldol reaction for the introduction of the stereocenter at C3. The practicality of this synthesis is demonstrated by the preparation of an ansatrienol derivative, representing a formal total synthesis of the ansatrienins.
Key words
aldol reaction - ansamycin antibiotics - macrolactamization - ring-closing metathesis - total synthesis
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References
Rüdiger Wittenberg, current address: DS-Chemie GmbH, Straubinger Straße 12, 28219 Bremen, Germany; Kai-Uwe Schöning, current address: Ciba Speciality Chemicals Inc., R-1059.4.04, 4002 Basel, Switzerland; Stefan Kamlage, current address: Institut für Organische Chemie, Freie Universität Berlin, Takustraße 3, 14195 Berlin, Germany.
20One major problem that arose during the oxidative cleavage of the boronic ester was the formation of furan 45 which may have originated from over oxidation of diol 26 and formation of the aldehyde 44 (Scheme [10] ). Lactol formation and elimination yields 45. This side reaction was fully suppressed, if H2O2 was slowly added to a well cooled solution of the boronate
31When other alcohols than allyl alcohol were employed we observed exchange of allyl in the alloc group by these alcohols.