780
Communications to the Editor
Chem. Pharm. Bull. 52(6) 780—782 (2004)
Vol. 52, No. 6
C-6-oxygen bond of the oxirane ring (route a). The bio-
mimetic-type total synthesis of capsanthin 2 was accom-
plished4) using regio- and stereoselective rearrangement of
the C15-epoxy dienal with a silyloxy group at C-3, as shown
in Chart 1 (route b).
First Total Synthesis of
Cucurbitaxanthin A Applying
Regioselective Ring Opening of
Tetrasubstituted Epoxides
There has been a report6) concerning the attempted synthe-
sis of cycloviolaxanthin, a carotenoid with a 3,6-epoxy end
group. Here we describe the first total synthesis of the 3,6-
epoxy-carotenoid cucurbitaxanthin A 1 (Chart 1) applying
biomimetic-type ring opening (route a) of the 3-hydroxy-C15-
epoxy dienonate and dienonitrile.
Yumiko YAMANO and Masayoshi ITO*
Kobe Pharmaceutical University; Motoyamakita-machi, Higashi-
nada-ku, Kobe 658–8558, Japan.
Received March 3, 2004; accepted April 5, 2004
First, we investigated the ring opening of epoxides 6a—f7)
(Chart 3, Table 1), which has a hydroxy group at C-3, toward
the synthesis of cucurbitaxanthin A 1. Treatment of epoxides
6a and 6b carrying a strong EWG with SnCl4 or the aminium
salt 108) resulted in the formation of a complicated mixture
including cyclopentyl ketones 9a and 9b (entries 1—3 in the
Table 1). In the case of epoxides 6c and 6d, which do not
have an EWG, the desired 3,6-epoxides 7c and 7d were
formed by the opening of the C-6-oxygen bond of the oxi-
rane ring and subsequent ring closing from the C-3-hydroxy
group (entries 5, 6). However, preferential migration of the
7,8-double bond to the attack of the C-3-hydroxy group gave
5,8-epoxides 8c and 8d as major products. Introduction of
weak EWGs (entries 8, 9) improved the yield of the desired
3,6-epoxides 7e and 7f.9) Formation of the 3,6-epoxides
would require both ease of ring opening at C-6 and difficult
migration of the 7,8-double bond. Thus in dienoate and
dienonitrile systems, the conjugated double bond would tend
to be retained in the original moieties.
The synthesis of cucurbitaxanthin A 1 was accomplished via
the C15-3,6-epoxides 7e and 7f prepared by regioselective ring
opening of the 3-hydroxy-5,6-epoxides 6e and 6f.
Key words cucurbitaxanthin A; 3,6-epoxide; tetrasubstituted epoxide;
ring opening; total synthesis
There are many xanthophylls that hypothetically are as-
sumed to be derived from 5,6-epoxy-carotenoids through
ring opening of the epoxy moiety. Cucurbitaxanthin A 1
(Chart 1) with a 3,6-epoxy-end group is isolated from both
the red paprika Capsicum annuum1,2) and pumpkin Cucurbita
maxima3) and capsanthin 2 with a k-end group is isolated
from the former. Both carotenoids are also considered2) to be
formed in nature from 5,6-epoxy-carotenoids.
From the previous results4) in the reaction of epoxides
3a—e with an olefinic group at C-65) (Chart 2) with Lewis
acid, we found that the direction of the oxirane ring cleavage
depended upon both the length of conjugated double bond
system and the electron-withdrawing ability of the sub-
stituents adjacent to the double bond. Epoxides 3a and 3d
carrying a strong electron-withdrawing group (EWG) pre-
dominantly provided the cyclopentyl ketones 5a and 5d, re-
spectively, via cleavage of the oxirane ring at the C-5 posi-
tion (route b), whereas 5,6-epoxides 3b, 3c, and 3e only gave
5,8-epoxides 4b, 4c, and 4e, respectively, via opening of the
As shown in Chart 4, epoxides 6e and 6f were prepared
from the known C10-epoxy aldehyde 12, which was recently
synthesized by Katsumura’s group10) via a Sharpless asym-
metric epoxidation of the corresponding allylic alcohol de-
rived from the optically active hydroxyketone 11.11) Em-
mons-Horner reaction of the aldehyde 12 with the phospho-
Chart 1
Chart 2
∗ To whom correspondence should be addressed. e-mail: m-ito@kobepharma-u.ac.jp
Chart 3
© 2004 Pharmaceutical Society of Japan