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SYNTHESIS OF CONFORMATIONALLY RESTRICTED AMINO ACIDS, PEPTIDES AND PEPTIDOMIMETICS BY CATALYTIC RING CLOSING METATHESIS

机译:催化环封闭分解法合成构象受限的氨基酸,肽和肽同质物

摘要

A method for synthesizing conformationally restricted amino acids, peptides, and peptidomimetics by ring closing metathesis. The method includes the steps of synthesizing a peptide precursor containing first and second unsaturated C-C bonds and contacting the peptide precursor with an RCM catalyst to yield a conformationally restricted peptide. Suitable peptide precursors may contain two or more unsaturated C-C bonds. These bonds may be olefinic bonds and may be contained in first and second alkenyl groups which may be allyl groups. The RCM catalyst may be a Ruthenium or Osmium carbene complex catalyst and more specifically, a Ruthenium or Osmium carbene complex catalyst that includes a Ruthenium or Osmium metal center that is in a +2 oxidation state, has an electron count of 16, and is pentacoordinated. The method may be carried out using solid-phase-peptide-synthesis techniques. In this embodiment, the precursor, which is anchored to a solid support, is contacted with an RCM catalyst and the product is then cleaved from the solid support to yield a conformationally restricted peptide.
机译:一种通过闭环易位合成构象受限的氨基酸,肽和拟肽的方法。该方法包括以下步骤:合成含有第一和第二不饱和C-C键的肽前体,并使该肽前体与RCM催化剂接触以产生构象受限的肽。合适的肽前体可包含两个或更多个不饱和C-C键。这些键可以是烯键,并且可以包含在可以是烯丙基的第一和第二烯基中。 RCM催化剂可以是钌或O卡宾络合物催化剂,更具体地,钌或O卡宾络合物催化剂包括处于+2氧化态的钌或O金属中心,电子数为16,并且是五配位的。 。该方法可以使用固相肽合成技术进​​行。在该实施方案中,将锚固在固体支持物上的前体与RCM催化剂接触,然后从固体支持物上裂解产物以产生构象受限的肽。

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