DIARYL ETHER AMINO ACIDS VIA DIELS-ALDER REACTIONS

Diels-Alder环加成反应将被用作合成路线 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， 作为异酪氨酸和环中存在的相关氨基酸单元， 肽抗生素K-13、OF 4949、布伐定和万古霉素。 烯酮以及 由L-或D-丝氨酸衍生物制备Eynone双烯亲体。 与芳氧基官能化的1，4-二烯的环加成以及随后的 芳构化将提供目标二芳基醚氨基酸。 模型 研究已经证明了这种方法用于合成 光学纯形式的异酪氨酸衍生物。 该方法还具有 可能导致β-羟基酪氨酸的合成 如万古霉素家族中存在的，通过立体选择性 中间体β-酮酪氨酸衍生物的还原。 肽类抗生素K-13、OF 4949-III的合成， 14-bouvardins的三元环（异酪氨酸）单元将在 其中环化步骤将涉及Diels-Alder环加成以形成 二芳基醚单元。 这些研究将包括编写 所需的三肽或二肽单元包含在N-和C-末端侧 链的二烯和亲二烯体组分所需的分子内 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，然后是涉及巴顿 脱羧-苯基硒化，得到芳香族产物，和（2） 使用丝氨酸衍生α-吡喃酮的逆电子需求Diels-Alder方法 和芳氧基取代的烯烃。 这些方法将用于 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.