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Recent Advances in Substrate-Controlled Asymmetric Induction Derived from Chiral Pool Α-Amino Acids for Natural Product Synthesis

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Recent Advances in Substrate-Controlled Asymmetric Induction Derived from Chiral Pool Α-Amino Acids for Natural Product Synthesis molecules Review Recent Advances in Substrate-Controlled Asymmetric Induction Derived from Chiral Pool α-Amino Acids for Natural Product Synthesis Seung-Mann Paek 1, Myeonggyo Jeong 2, Jeyun Jo 2, Yu Mi Heo 1, Young Taek Han 3 and Hwayoung Yun 2,* 1 College of Pharmacy, Research Institute of Pharmaceutical Science, Gyeongsang National University, Jinju daero, Jinju 52828, Korea; [email protected] (S.-M.P.); [email protected] (Y.M.H.) 2 College of Pharmacy, Pusan National University, Busan 46241, Korea; [email protected] (M.J.); [email protected] (J.J.) 3 College of Pharmacy, Dankook University, Cheonan 31116, Korea; [email protected] * Correspondence: [email protected]; Tel.: +82-51-510-2810; Fax: +82-51-513-6754 Academic Editors: Carlo Siciliano and Constantinos M. Athanassopoulos Received: 15 June 2016; Accepted: 18 July 2016; Published: 21 July 2016 Abstract: Chiral pool α-amino acids have been used as powerful tools for the total synthesis of structurally diverse natural products. Some common naturally occurring α-amino acids are readily available in both enantiomerically pure forms. The applications of the chiral pool in asymmetric synthesis can be categorized prudently as chiral sources, devices, and inducers. This review specifically examines recent advances in substrate-controlled asymmetric reactions induced by the chirality of α-amino acid templates in natural product synthesis research and related areas. Keywords: chiral pool; α-amino acid; natural product; total synthesis; asymmetric induction 1. Introduction The chiral pool approach is highly attractive in the asymmetric total synthesis of bioactive natural products with diverse and complex architectures [1,2]. This strategy is one of the best methods available to synthetic organic chemists for establishing pivotal stereocenters in optically active compounds [3–7]. The chiral pool is a versatile tool, comprising naturally occurring chiral molecules such as carbohydrates, amino acids, terpenes, alkaloids, and hydroxyacids [2,6]. They include enantiomerically enriched species that can be synthetically transformed into the desired target molecules. Chiral pool materials are also inexpensive and commercially available, making them adequate for use in accessing natural products and bioactive compounds [2]. The usage of the chiral pool in asymmetric synthesis can be classified in three general categories, as shown in Figure1: (a) chiral sources, used as building blocks containing built-in stereocenters for target molecules; (b) chiral devices, employed as useful tools for enantioselective catalysts and auxiliaries; and (c) chiral inducers, applied to the generation of new stereocenters in a substrate-controlled manner [1–7]. The chiral inducer strategy is a highly efficient method to exploit advantages of both the chiral source and device approach at the same time. The specific aim of this review is to present useful applications of enantiomerically enriched α-amino acids as substrate-controlled asymmetric inducers in natural product synthesis from 2011 to May 2016. Chirally pure α-amino acids are very useful materials due to diversity of functional group and ease of commercial use [7]. The α-amino acids described in this review are illustrated in Figure2. The use of amino acids as chiral sources and devices for asymmetric synthesis is not covered. Also, synthesis of acyclic or cyclic peptide natural products is not included. Molecules 2016, 21, 951; doi:10.3390/molecules21070951 www.mdpi.com/journal/molecules Molecules 2016, 21, 951 2 of 13 Molecules 2016, 21, 951 2 of 13 Molecules 2016, 21, 951 2 of 13 Molecules 2016, 21, 951 2 of 13 FigureFigure 1.1. Three categoriescategories ofof chiralchiral poolpool useuse inin asymmetricasymmetric synthesis.synthesis. Figure 1. Three categories of chiral pool use in asymmetric synthesis. Figure 1. Three categories of chiral pool use in asymmetric synthesis. Figure 2. Representative α‐amino acids. Figure 2. Representative αα‐-aminoamino acids. Figure 2. Representative α‐amino acids. 2. Chiral Pool: Proline 2. Chiral Pool: Proline 2. Chiral Pool: Proline 2. ChiralRecently, Pool: a Proline wide range of natural and non‐natural product syntheses using proline as the chiral pool Recently, a wide range of natural and non‐natural product syntheses using proline as the chiral pool materialRecently, in a substrate a wide range‐controlled of natural manner and non-naturalhave been reported. product synthesesSuh et al. usingsynthesized proline polyhydroxylated as the chiral pool materialRecently, in a substrate a wide range‐controlled of natural manner and nonhave‐natural been reported. product synthesesSuh et al. usingsynthesized proline polyhydroxylated as the chiral pool materialindolizidine in a substrate-controlledalkaloids, 1‐deoxy‐6,8a manner‐di‐epi have‐castanospermine been reported. (4 Suh) and et 1 al.‐deoxy synthesized‐6‐epi‐castanospermine polyhydroxylated (7), materialindolizidine in a alkaloids,substrate‐ controlled1‐deoxy‐6,8a manner‐di‐epi have‐castanospermine been reported. (4 )Suh and et 1 ‐al.deoxy synthesized‐6‐epi‐castanospermine polyhydroxylated (7), indolizidinethat can act alkaloids,asalkaloids, selective 1-deoxy-6,8a-di- 1 ‐α‐deoxyglycosidase‐6,8a‐diepi ‐inhibitorsepi-castanospermine‐castanospermine [8,9]. L‐Proline (4) ( and4) and was 1-deoxy-6- 1 ‐utilizeddeoxyepi‐6 as-castanospermine‐epi a‐ platformcastanospermine to construct (7), that(7), that can act as selectiveα α‐glycosidase inhibitors [8,9]. L‐Proline was utilized as a platform to construct thatcanthe actindolizidinecan as act selective as selective skeleton,-glycosidase α‐glycosidase as shown inhibitors in inhibitors Scheme [8,9 ].1.[8,9]. L(-ProlineE) ‐LSilyl‐Proline enol was was utilizedether utilized 2, obtained as a as platform a platform from to L‐ construct prolineto construct via the a the indolizidine skeleton, as shown in Scheme 1. (E)‐Silyl enol ether 2, obtained from L‐proline via a indolizidineknown protocol skeleton, [10,11], as shown underwent in Scheme an 1aza.( E‐Claisen)-Silyl enol rearrangement ether 2, obtained to produce from L-proline the corresponding via a known theknown indolizidine protocol skeleton, [10,11], underwentas shown in an Scheme aza‐Claisen 1. (E)‐ Silylrearrangement enol ether 2 to, obtained produce from the Lcorresponding‐proline via a protocol9‐membered [10,11 lactam], underwent 3 in 66% an yield. aza-Claisen This transformation rearrangement was to produceimpressive the not corresponding only because 9-membered it created a known9‐membered protocol lactam [10,11], 3 in 66%underwent yield. This an transformationaza‐Claisen rearrangement was impressive to producenot only becausethe corresponding it created a lactamnew stereogenic3 in 66% yield. center This through transformation a 6‐membered was transition impressive state, not but only also because because it createdit afforded a new a cis stereogenic‐azoninone 9new‐membered stereogenic lactam center 3 inthrough 66% yield. a 6‐membered This transformation transition state, was but impressive also because not itonly afforded because a cis it‐azoninone created a centerframework through simultaneously. a 6-membered The transition final product state, 4 was but alsoafforded because after it subsequent afforded a transformations.cis-azoninone framework Similarly, newframework stereogenic simultaneously. center through The a final 6‐membered product 4 transition was afforded state, after but subsequentalso because transformations. it afforded a cis‐azoninone Similarly, simultaneously.(Z)‐silyl enol ether The 5 was final converted product into4 was trans afforded‐azoninone after 6 under subsequent microwave transformations.‐assisted conditions. Similarly, It is framework(Z)‐silyl enol simultaneously. ether 5 was converted The final productinto trans 4 was‐azoninone afforded 6 after under subsequent microwave transformations.‐assisted conditions. Similarly, It is (noteworthyZ)-silyl enol that ether the5 synwas‐diol converted moiety intoof thetrans azoninone-azoninone skeleton6 under was microwave-assisted created via chiral communication conditions. It isof (noteworthyZ)‐silyl enol that ether the 5 synwas‐diol converted moiety ofinto the trans azoninone‐azoninone skeleton 6 under was microwavecreated via‐ assistedchiral communication conditions. It ofis noteworthythe L‐proline that that stereocenter the the synsyn‐diol-diol during moiety moiety aza of of‐ theClaisen the azoninone azoninone rearrangement skeleton skeleton was‐induced was created created ring via viaexpansion. chiral chiral communication communication The transition of the L‐proline stereocenter during aza‐Claisen rearrangement‐induced ring expansion. The transition ofstates the Lin-proline both these stereocenter conversions during made aza-Claisen it possibl rearrangement-inducede for the sole chiral center ring of expansion. amino acid The 1 transitionto induce thestates L‐proline in both stereocenter these conversions during made aza‐Claisen it possibl rearrangemente for the sole‐ inducedchiral center ring expansion.of amino acid The 1 transitionto induce statesadditional in both chirality these conversionsin cis or trans made azoninones it possible 3 and for 6. the sole chiral center of amino acid 1 to induce statesadditional in both chirality these conversionsin cis or trans made azoninones it possibl 3 ande for 6 .the sole chiral center of amino acid 1 to induce additional chirality in cis or trans azoninones 3 and 6. Scheme 1. Total syntheses of castanospermines 4 and 7. Scheme 1. Total syntheses
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