- Synthesis of (-)-terpestacin via catalytic, stereoselective fragment coupling: Siccanol is terpestacin, not 11-epi-terpestacin
-
(-)-Terpestacin (1a, naturally occurring enantiomer) and (+)-11-epi-terpestacin (1b) were prepared using catalyst-controlled, stereoselective intermolecular reductive couplings of alkyne 4 and aldehyde 5. Related to enantioselective methods developed in o
- Chan, Johann,Jamison, Timothy F.
-
-
Read Online
- Total synthesis of discodermolide: Optimization of the effective synthetic route
-
An efficient and modulable total synthesis of discodermolide (DDM), a unique marine anticancer polyketide is described including related alternative synthetic approaches. Particularly notable is the repeated application of a crotyltitanation reaction to yield homoallylic (Z)-O-ene-carbamate alcohols with excellent selectivity. Advantage was taken of this reaction not only for the stereocontrolled building of the syn-anti methyl-hydroxy- methyl triads of DDM, but also for the direct construction of the terminal (Z)diene. Of particular interest is also the installation of the C13=C14 (Z)-double bond through a highly selective dyotropic rearrangement. The preparation of the middle C8-C14 fragment in two sequential stages and its coupling to the C1-C7 moiety was a real challenge and required careful optimization. Several synthetic routes were explored to allow high and reliable yields. Due to the flexibility and robust character of this approach, it might enable a systematic structural variation of DDM and, therefore, the elaboration and exploration of novel discodermolide structural analogues.
- De Lemos, Elsa,Poree, Francois-Hugues,Bourin, Arnaud,Barbion, Julien,Agouridas, Evangelos,Lannou, Marie-Isabelle,Commercon, Alain,Betzer, Jean-Francois,Pancrazi, Ange,Ardisson, Janick
-
experimental part
p. 11092 - 11112
(2009/11/30)
-
- Enantioselective synthesis of (-)-terpestacin and structural revision of siccanol using catalytic stereoselective fragment couplings and macrocyclizations
-
(-)-Terpestacin (1, naturally occurring enantiomer) and (+)-11-epi-terpestacin (2) were prepared using catalyst-controlled, stereoselective, intermolecular reductive coupling reactions of alkyne 9 and aldehyde 10, affording allylic alcohols 42 or 11-epi-42 in a 3:1 ratio (or 1:3 depending on the enantiomer of ligand 41a used). These stereoselective fragment couplings were instrumental in confirming that "siccanol" is not 11-epi-terpestacin but, in fact, is (-)-terpestacin itself. Several intramolecular alkyne-aldehyde reductive coupling approaches to 1 and 2 were also investigated and are discussed herein.
- Chan, Johann,Jamison, Timothy F.
-
p. 10682 - 10691
(2007/10/03)
-