Pergamon Tetrahedron: Asymmetry 9 (1998) 4055–4071
TETRAHEDRON:
ASYMMETRY
Studies towards the total synthesis of taxoids: a rapid entry into
bicyclo[6.4.0]dodecane ring system. Part 1
Siméon Arseniyadis,
a,*
María del Rosario Rico Ferreira,
a
José Quílez del Moral,
a
José Ignacio Martín Hernando,
a
Pierre Potier
a
and Loïc Toupet
b
a
Institut de Chimie des Substances Naturelles, CNRS, F-91198, Gif-sur-Yvette, France
b
URA 804 au CNRS, Université de Rennes I, F-35042, Rennes, France
Received 5 October 1998; accepted 26 October 1998
Abstract
We report a short and stereocontrolled synthesis of the taxoid BC-subunit (+)-5 embodying the whole carbon
framework and most of the required oxygen functionalities for further elaboration. Enantiomeric purity was secured
at an early stage by resolution involving derivatization with (S)-2-acetoxypropionyl chloride on (±)-10b. © 1998
Elsevier Science Ltd. All rights reserved.
1. Introduction
Previous studies from this laboratory concerned with the synthesis of taxoid analogues have revealed
a three-reaction based strategy, the aldol–annulation–fragmentation methodology,
1
for stereoselectively
constructing taxoid
2
BC-subunits. These early studies have established the feasibility of producing the
20-carbon framework of the taxoid diterpene skeleton I in relatively few steps from inexpensive starting
materials.
We detail herein a full account of our approach, built around methylcyclopentenone, to which were
attached the atoms destined to become the taxoid subunit embodying the whole carbon framework and
suitable oxygen functionalities. Methyl acetoacetate, methyllithium, benzoic acid, methyl iodide and
formalin together with methylcyclopentenone would provide the entire taxoid diterpene skeleton using
our three-reaction sequence.
*
Corresponding author. E-mail: simeon.arseniyadis@icsn.cnrs-gif.fr
0957-4166/98/$ - see front matter © 1998 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(98)00434-0