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1
Tetrahedron
A facile approach for the total synthesis of neurotrophic diyne tetraol petrosiol A and
petrosiol E
Gangadhar Pamarthi, A. Sathish Reddy, Srihari Pabbaraja
Division of Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad – 500007, India
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
The first total synthesis of neurotrophic diacetylenic tetraol, petrosiol A and stereoselective total
synthesis of petrosiol E was accomplished. The total synthesis involves Cadiot-Chodkiewicz
coupling reaction as the key step for petrosiol A. The diastereorich chiral alcohol (third chiral
center) was synthesized from CBS mediated stereoselective ketone reduction reaction for
petrosiol E. Of the three chiral centers, the two chiral centers are originated from (+)-diethyl L-
tartrate and the third chiral center was generated by an addition reaction of lithium
trimethylsilylacetylide leading to two diastereomers which were used for the synthesis of both
the natural products and their diastereomer C6-epi-petrosiol A and C6-epi-petrosiol E
respectively.
Available online
Keywords:
polyacetylene
neurotrophic
Cadiot Chodkiewicz
Swern oxidation
CBS reduction
2009 Elsevier Ltd. All rights reserved.
1. Introduction
The first contribution was from our own group6 wherein we
have accomplished the total synthesis of petrosiol D in a linear
Polyacetylene containing molecules continue to attract
significant attention due to their impressive biological properties
such as anti-inflammatory, antimicrobial, antitumor, antiviral,
cytotoxic, neurotrophic and phytotoxic properties.1 For example
panaxydol2 1 displayed antiproliferative effects against malignant
cells and panaxytriol3 2 displayed inhibitory activity against MK-
1 cells with IC50 8.5 ng/mL. Very often the scarce availability of
natural products becomes the bottleneck for investigating their
further biological properties, and this challenge can be easily
overcome by their total synthesis. For example, our recent
attempt for the total synthesis of diacetylene natural products
oploxyne A (3) and B (4) not only lead to the accessibility of the
materials but also ended up with structural revision of the natural
product oploxyne B.4 Also, on further investigation these
molecules were found to display cytotoxicity against
neuroblastoma and prostate cancer cell lines. In continuation to
our studies on the total synthesis of natural products and their
analogues for CNS activities,5 we have recently accomplished the
first total synthesis of petrosiol D 5,6 which was isolated from an
extract of the Okinawan sponge Petrosia strongylata along with
four other acetylene metabolites petrosiol A-C (6-8) (Figure 1)
and petrosiol E 9 by Ojika et al.7 In biological aspects, these
compounds induced nerve growth factor (NGF)-like neuronal
differentiation of PC12 cells and in terms of cytotoxicity, the IC50
value of petrosiol A was found to be 5.4 µM in the MTT assay
and 0.22 µM for A431(human epidermoid) cell line.7 So far there
have been only two synthetic contributions for petrosiols.
fashion and the second contribution was from Yoguo Du et al.
wherein they have accomplished the total synthesis of (-)-
petrosiol E following a chiron approach starting from D-xylose.8
Herein, we describe the total synthesis of petrosiol A, petrosiol E
and their diastereomers starting from the readily available
material (+)-Diethyl L-tartrate.
Figure 1: Diacetylene polyol compounds
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Corresponding author. Tel.: +914027191815; fax: +914027160512; e-mail: srihari@iict.res.in