Ljungqvist A, Bowers C Y, Folkers K
Institute for Biomedical Research, University of Texas, Austin.
Int J Pept Protein Res. 1993 May;41(5):427-32. doi: 10.1111/j.1399-3011.1993.tb00461.x.
N-Ac-D-O-phenyltyrosine was synthesized via the corresponding azlactone. Resolution of the DL methyl esters was achieved by Subtilisin Carlsberg. Treatment with palladium(II) acetate in trifluoroacetic acid converted N-Ac-D-O-phenyltyrosine into N-Ac-D-3-(2-dibenzofuranyl)alanine. These two amino acids were incorporated instead of N-Ac-D-2-Nal into position 1 of the LHRH-antagonist (N-Ac-D-2-Nal1, D-p-ClPhe2, D-3-Pal3, c-PzACAla5, D-PicLys6, ILys8,D-Ala10)-LHRH. The more rigid N-Ac-D-3-(2-dibenzofuranyl)alanine was structurally more effective than N-Ac-D-O-phenyltyrosine; the AOAs for the corresponding analogs were 82 and 38%, respectively, at 0.5 micrograms. Replacement of c-PzACAla in position 5 by O-phenyltyrosine significantly decreased potency.
N-乙酰-D-O-苯丙氨酸通过相应的恶唑酮合成。利用嗜热栖热菌蛋白酶实现了DL甲酯的拆分。在三氟乙酸中用乙酸钯（II）处理将N-乙酰-D-O-苯丙氨酸转化为N-乙酰-D-3-（2-二苯并呋喃基）丙氨酸。这两种氨基酸取代了N-乙酰-D-2-萘丙氨酸被引入到促性腺激素释放激素拮抗剂（N-乙酰-D-2-萘丙氨酸1、D-对氯苯丙氨酸2、D-3-吡啶丙氨酸3、环戊基丙氨酸5、D-吡啶赖氨酸6、异亮氨酸8、D-丙氨酸10）-促性腺激素释放激素的第1位。刚性更强的N-乙酰-D-3-（2-二苯并呋喃基）丙氨酸在结构上比N-乙酰-D-O-苯丙氨酸更有效；相应类似物在0.5微克时的抗排卵活性分别为82%和38%。用O-苯丙氨酸取代第5位的环戊基丙氨酸显著降低了效力。
