Organic Chemistry of Drug Synthesis. Volume 7

group is next converted to the activated imidazolide by reaction with
carbonyl diimidazole. Condensation of this intermediate with pyrrolidine
gives the corresponding amide. Removal of the silyl protection groups
with fluoride leads toecalcidine( 111 ).^21

RO OR R = Si(CH(CH 3 )) 2 RO OR

SO 2

SO 2 1. O2. heat^3

RO OR

CH=O

106 107 108

RO OR

109

1. NaBH 4


2. CH 3 SO 2 Cl

OSOCH 3

1.

2. NaOH3. HCl

CO 2 C 2 H 5

CO 2 C 2 H 5

RO OR

110

CO 2 H

1. CDI,
   2.F–

HO OH

111

O

N

HN

3. POLYCYCLIC COMPOUNDS

A sequiterpinoid fulvene from the Jack O’Lantern mushroom was found
some years ago to show very promising antitumor activity in a number
ofin vitroassays. This compound, Iludin S ( 112 ) was, however, found
to be too toxic in follow-upin vivotests to be considered for further
development. The semisynthetic analogueirofulven( 114 ) is far better tol-
erated and has been taken to the clinic where it demonstrated activity
against several tumors. Though a total synthesis has been published,^22
the compound is most efficiently prepared by semisynthesis from Iludin
S itself. Treatment of the natural product with dilute acid leads to loss of
the elements of water and formaldehyde in what may be considered a
reverse hydroformylation reaction to yield intermediate 113. Reaction of
that product with formaldehyde in dilute acid in essence reverses the last
reaction, though with a different regiochemistry. Formaldehyde thus

38 ALICYCLIC COMPOUNDS