polypeptide; the drug does so by stimulating secretion of growth hormone
from the pituitary gland. This agent has shown promising results in the
clinic. The reaction sequence for its preparation begins with acylation of
the amino group in spiroindoline ( 119 ) with carbobenzyloxy chloride to
afford 120. The methyl group on the piperidine ring in this product is
then removed using a modern version of the von Braun reaction ( 121 ).
Acylation of this product with thet-BOC derivative of benzyloxyserine
( 122 ) using standard peptide-forming condition leads to the amide ( 123 ).
Treatment of that intermediate with trifuoroacetic acid removes the
t-BOC protecting group to reveal the free primary amine ( 124 ). The
peptide-like side chain is next extended by acylation witht-BOC protected
aminoisobutyric acid ( 125 ) to give 126. Catalytic hydrogenation next
removes the Cbz group that has protected the indoline nitrogen through
the preceding steps ( 127 ). Reaction of 127 with methanesulfonyl chloride
gives the corresponding sulfonamide. Trifluroacetic acid then removes the
remainingt-BOC group to afford 128.^17
Compounds whose structures include a quinone moiety have been inten-
sively investigated as potential antitumor agents. At least two quinones,
mitomycin C and diaziquone, that have found their way to the clinic.
These compounds in addition include a reactive aziridine ring. A recent
entry that incorporates both those features, apaziquone ( 135 ), also
known as EO9, may be viewed as an oxidized indole. In the key reaction
of a succinct synthesis to this agent, quinone 129 is allowed to react with
129OOBrCH 3 O CO 2 CH 3
HN
CH 3+130OOCH 3 O
N
OCH 3OCH 3CO 2 CH 3131DDQOOCH 3 O
NCH=OCO 2 CH 3CO 2 CH 3CO 2 CH 3132CH 3 CH 3(CH 3 O) 2 P0CH 2 CO 2 CH 3
LiBr, Et 3 N
OOCH 3 O
N133CH 3DiBAL-HOOCH 3 O
N134CH 3 CH 3OHOHOON
N135OHOHNHtheN-methylenamine from 4-methoxyacetoacetate 130 to form the fused
pyrrole ring in a single step. The reaction can be rationalized by assuming
that the first step involves displacement (or addition–elimination) of
154 FIVE-MEMBERED HETEROCYCLES FUSED TO ONE BENZENE RING