Studies On The Synthesis And Peptide Linkage Of Steroid

Dutasteride (a new kind of anti-benign prostatic hyperplasia drug), 17β-N-(2,5-bis(trifluoromethyl))phenylcarbamoyl-4-aza-5α-androst-1-en-3-one, was synthesized by employing amidation and DDQ/BSTFA oxidation as a pivotal step from the starting material 3-oxo-4-androstene-17-β-carboxylic acid. Dutasteride was synthesized by the total yield 23%. The structure of the target molecule and the key intermediates was confirmed by IR, 1H NMR, 13C NMR and MS in our experiments. The route does not require high pressure and high temperature that may be applied to industrial production.Similarly, Finasteride (MK-906), 17β-(N-tert-butylcarbamoyl)-4-aza-5α- androst -1- en-3-one, was synthesized by employing amidation, NaBH3CN reduction and DDQ/BSTFA oxidation as a pivotal step from the starting material 3-oxo-4-androstene-17-β-carboxylic acid. Finasteride was synthesized by the total yield 29%. The structure of the target molecule and the key intermediates was confirmed by IR, 1H NMR, 13C NMR and MS in our experiments. The route does not require high pressure and high temperature that may be applied to industrial production.Thymopentin (TP-5), thymic hormone analog corresponding to residues 32-36 of thymopoietin. Here, we describe a novel approach for the synthesis of thymopentin using solid phase method. The synthesis of protected thymopentin was carried out entirely using a conventional Fmoc protocol and self-made synthesizer. Thymopentin was synthesized with high yield (yield 71.3%) using this procedure. This novel approach provides a strategy for the rapid and efficient large-scale synthesis of thymopentin for pharmaceuticals. The structure of the key intermediate and target molecule was confirmed by ESI-MS, elementary analysis, IR, 1H-NMR and 13C-NMR spectra in our experiments.Similarly, Thymopentin derivetive (septapeptide) has been prepared by the solid-phase peptide synthesis method in which stepwise and segment condensation are involved. The solid phase strategy in which using the Fmoc deprotected with 20% piperidine/DMF. Finaly, TFA solution have been used as the agent which cleaves the goal peptide from the resin. The total yield is 61.2% (calculated from the first amino acid anchored to resin). The structure of the key intermediate and target molecule was confirmed by ESI-MS, elementary analysis, IR, 1H-NMR and 13C-NMR spectra in our experiments. In this study, we found that both of thymopentin derivetive(i.e. septapeptide)as well as thymopentin could promote T cell proliferation and increase of E-rose fomation cells.Finally, the reaction of dutasteride and finasteride with acetyl chloride as a model reaction was examined. The results showed that the products of N-acetylated of finasteride and dutasteride were compound 18 and 12 under such a condition, respectively. After the accomplishment of the reaction for the N-acetylated of dutasterid and finasteride, we examined the reaction of finasteride and dutasteride with pidotimod, respectively. The results showd that the main product of dutasteride with pidotimod was compound 20 and the main product of finasteride with pidotimod was compound 14. A summary account, the reaction of finasteride and dutasteride with peptide was possible.