?\larch 5, 19tiO
COhlhlUNICATIONS T O T H E
tion into the syn acid IITa(1n.p. 197.5-200'; found: C, 66.57; HI 5.54; C1, 8.83; A",:" 342 mp, log e 4.14) and the anti acid IVb (m.p. 179-181'; found: C, 66.68; HI 5.41; A,M:xOH 342 mp, log e 4.14). Relative stereochemical assignments were made on the basis that cyclization to syn product IVa occurred more rapidly and in higher yield (30-35Yo) than did closure to anti isomer IVb (10-15%),2 and on the fact that treatment of IVa with diazomethane produced the previously described syn ester 1Vc.I C1 c- x c -x
&yyt
@' \
0
\
\
\
0 0 CHz
0 ti0
CH2 C6H5
HO
C6H5
It'b X = GH Vb X = CH(COOC2HI)z
IVa X = OH IVC X = OCBz Va X = CH(COOCX&
Conversion of syn acid IVa to acylmalonate Val and then cyclization with sodium hydride in refluxing toluene gave the tetracyclic ester V13s4 in 30% yield (m.p. 151-154'; found: C, 66.01; H I m s x N82B407 , 440, 340, 265 mp, log e, 4.20, 5.54; xu.'" 3.98, 4.05). Hydrogenolysis of the benzyl group over 10% Pd/C yielded phenol VI1 (m.p. 162-4", X Om .a1xM NmB'O, , 450, 270 mp, log e, 4.39, 4.05). Fusion of the latter with ammonium formate a t 140°, and hydrolysis with hydrochloric acid led in low yield to racemic amide I (12;; 2.93, 6.30, 6.86, 7.66, 8.61, 12.10, 12.60 p , ";::A: NaoH(NeoH) 495, 469, 375, 262 m,u). Natural 6-deniethyl-7-chlorotetracycline5 was converted to the 6-deoxy derivative by catalytic reduction.6 Zinc dust reduction' of the dimethylamino and 12a hydroxyl groups gave optically active amide I (found: C, 58.69; H, 4.04; N , 3.88). Comparison of this material with the synthetic product by paper chromatography, infrared and (2) A total of six conformations can be drawn for the transition states leading t o IVa and IVb. Four of these each possess a minimum of two 1,3-diaxial carbon-hydrogen interactions and may be regarded a s unlikely. For the remaining two, which would lead t o intermediate diketones ia and ib, t h a t giving ia involves one less 1,3-diaxial carbonhydrogen interaction than t h a t giving ib, hence formation of ia and thus IVa should be kinetically favored.
p&R R'
0 0 CH2
0
C6H5
io R = H
R'=CH2COOH
i b R=CH2COOH R'=H (3) Zinc dust distillation of t h e ester gave naphthacene. (4) Spectroscopic evidence indicates t h a t , under identical reaction conditions, t h e ani; acylmalonate Vb fails t o yield a tetraryclic cotn-
pound. ( 5 ) (a) J . I
