TY - JOUR
T1 - Transformation of penicillins into 3-substituted Δ3-cephems through addition/cyclization of allenecarboxylates
AU - Tanaka, Hideo
AU - Sumida, Shin Ichi
AU - Kameyama, Yutaka
AU - Sorajo, Koichi
AU - Wada, Isao
AU - Torii, Sigeru
PY - 1996/12/1
Y1 - 1996/12/1
N2 - A straightforward synthesis of Δ3-cephems 2 bearing heteroatom substituents directly attached to C(3)-position was performed successfully by a sequential addition/cyclization reaction of allenecarboxylate 4 derived from eithen penicillin 1. Upon treatment of the allenecarboxylate 4 with morpholine, pyrrolidine, sodium azide, and 5-methyl-1,3,4-thiadiazole-2-thiol in DMF in the presence of calcium chloride, the addition/cyclization reaction proceeded smoothly to afford the corresponding 3-substituted Δ3-cephems 2a-e. Reaction of the allenecarboxylate 4 with lithium chloride in NMP (N-methyl-2-pyrrolidone) in the presence of aluminum chloride afforded 3-chloro-Δ3-cephem 2f, while without aluminum chloride, 3-phenylsulfonyl-Δ3-cephem 2e was mainly obtained. The 3-sulfenyl-Δ3-cephems 12 were prepared by a similar addition/cyclization reaction of allenecarboxylates 10 with a catalytic amount of thiolates. The sulfenyl moieties attached at the sulfur atom of the C(4)-substituent of 10 were introduced at the C(3)-position of the cephem framework 2.
AB - A straightforward synthesis of Δ3-cephems 2 bearing heteroatom substituents directly attached to C(3)-position was performed successfully by a sequential addition/cyclization reaction of allenecarboxylate 4 derived from eithen penicillin 1. Upon treatment of the allenecarboxylate 4 with morpholine, pyrrolidine, sodium azide, and 5-methyl-1,3,4-thiadiazole-2-thiol in DMF in the presence of calcium chloride, the addition/cyclization reaction proceeded smoothly to afford the corresponding 3-substituted Δ3-cephems 2a-e. Reaction of the allenecarboxylate 4 with lithium chloride in NMP (N-methyl-2-pyrrolidone) in the presence of aluminum chloride afforded 3-chloro-Δ3-cephem 2f, while without aluminum chloride, 3-phenylsulfonyl-Δ3-cephem 2e was mainly obtained. The 3-sulfenyl-Δ3-cephems 12 were prepared by a similar addition/cyclization reaction of allenecarboxylates 10 with a catalytic amount of thiolates. The sulfenyl moieties attached at the sulfur atom of the C(4)-substituent of 10 were introduced at the C(3)-position of the cephem framework 2.
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U2 - 10.1246/bcsj.69.3651
DO - 10.1246/bcsj.69.3651
M3 - Article
AN - SCOPUS:0030478250
VL - 69
SP - 3651
EP - 3658
JO - Bulletin of the Chemical Society of Japan
JF - Bulletin of the Chemical Society of Japan
SN - 0009-2673
IS - 12
ER -