DIARYL ETHER AMINO ACIDS VIA DIELS ALDER REACTIONS

Diels-Alder环加成反应将作为合成路线应用 用于制备二芳基醚。一个主要目标将是 光学活性β-(二芳基醚)-α-氨基酸的制备 作为环中存在的异剂量酪氨酸和相关的氨基酸单元 多肽抗生素K-13、OF4949、布瓦丁和万古霉素。Enone和 将从L-或D-丝氨酸衍生物制备依诺酮型双烯烃化合物。 芳氧基功能化1，4-二烯的环加成反应及其后续反应 芳构化将提供目标二芳基醚氨基酸。型号 研究表明，这种方法在合成有机化合物方面具有潜力。 光学纯形式的等剂量酪氨酸衍生物。这种方法还具有 合成β-羟基酪氨酸的可能性 存在于万古霉素家族中的衍生物，通过立体选择性 中间体β-酮基酪氨酸衍生物的还原。 多肽抗生素K-13、OF4949-III的合成 将在#年研究布瓦丁的14元环(异剂量酪氨酸)单元 该环化步骤将涉及Diels-Alder环加成以形成 二芳基醚单元。这些研究将涉及准备 N-末端和C-末端所需的三肽或二肽单元 分子内所需的二烯和亲二烯组分的链 Diels-Alder反应。 光学活性苯甘氨酸的两条合成路线 将研究Diels-Alder方法。这些措施将涉及(1) 1，3-二芳氧基二烯与丝氨酸衍生的a， 6-不饱和酯和涉及Barton的反应序列 脱羧基-苯亚硒化反应生成芳香族产物，以及(2) 丝氨酸衍生α-吡喃酮的反电子需求Diels-Alder方法 和芳氧基取代的烯烃。这些方法将应用于 万古霉素核心三芳基二醚三肽单元的合成。

The Diels-Alder cycloaddition reaction will be applied as a synthetic route for preparation of diaryl ethers. A major objective will be the preparation of optically active beta-(diaryl ether)-alpha-amino acids, such as isodityrosine and related amino acid units as present in the cyclic peptide antibiotics K-13, OF4949, bouvardin, and vancomycin. Enone and eynone dienophiles will be prepared from L- or D-serine derivatives. Cycloaddition with aryloxy functionalized 1,4-dienes and subsequent aromatization will provide the target diaryl ether amino acids. Model studies have demonstrated the potential of this method for the synthesis of isodityrosine derivatives in optically pure form. This approach also has the potential to lead to the synthesis of beta-hydroxy tyrosine derivatives, as present in the vancomycin family, by stereoselective reduction of an intermediate beta-keto tyrosine derivative. The synthesis of the peptide antibiotics K-13, OF4949-III, and the 14-membered cyclo(isodityrosine) unit of the bouvardins will be studied in which the cyclization step will involve a Diels-Alder cycloaddition to form the diaryl ether unit. These studies will involve preparation of the required tri- or dipeptide units containing in the N- and C-terminal side chains the diene and dienophile components needed for the intramolecular Diels-Alder reaction. Two routes to the synthesis of optically active phenylglycines by Diels-Alder methodology will be studied. These will involve (1) cycloaddition of 1,3-diaryloxy dienes with a serine-derived a, 6-unsaturated ester followed by a reaction sequence involving a Barton decarboxylation-phenylselenation leading to aromatic product, and (2) an inverse electron demand Diels-Alder method using a serine-derived a-pyrone and an aryloxy-substituted alkene. These methods will be applied for a synthesis of the core triaryl diether tripeptide unit of vancomycin.