- Efficient diastereoselective synthesis of cis-2-amino-1-indanol derivatives and cis- and trans-1-amino-2-indanol via Pd-catalyzed hydrogenation
-
(±)-cis-2-amino-1-indanol was diastereoselectively synthesized from 1,2-indanedion-2-oxime in ethanol at 25 °C under 10% Pd/C-catalyzed hydrogenation conditions. Under the same hydrogenation condition, 1,2-indanedion-2-oxime and their derivatives having one and/or two electron-donating groups in aliphatic or aromatic part of indanyl ring were diastereoselectively reduced to racemic cis-2-amino-1-indanol derivatives. From 1,2-indanedion-1-oxime, (±)-trans-1-amino-2-indanol was obtained in ethanol at 25 °C over a 10% Pd/BaSO4 catalyst. In contrast, the 10% Pd/BaSO4-catalyzed hydrogenation reaction in ethanol at 45 °C afforded cis-1-hydroxyamino-2-indanol from 1,2-indanedion-1-oxime, followed by reduction to form (±)-cis-1-amino-2-indanol. The diastereoselectivity of β-aminoindanols was dependent on the Pd catalyst, reaction temperature, and pH of the reaction medium.
- Nguyen, Thi Ha,Ma, Eunsook
-
supporting information
p. 3717 - 3728
(2021/11/01)
-
- Enantioselective Cascade Biocatalysis for Deracemization of Racemic β-Amino Alcohols to Enantiopure (S)-β-Amino Alcohols by Employing Cyclohexylamine Oxidase and ω-Transaminase
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Optically active β-amino alcohols are very useful chiral intermediates frequently used in the preparation of pharmaceutically active substances. Here, a novel cyclohexylamine oxidase (ArCHAO) was identified from the genome sequence of Arthrobacter sp. TYUT010-15 with the R-stereoselective deamination activity of β-amino alcohol. ArCHAO was cloned and successfully expressed in E. coli BL21, purified and characterized. Substrate-specific analysis revealed that ArCHAO has high activity (4.15 to 6.34 U mg?1 protein) and excellent enantioselectivity toward the tested β-amino alcohols. By using purified ArCHAO, a wide range of racemic β-amino alcohols were resolved, (S)-β-amino alcohols were obtained in >99 % ee. Deracemization of racemic β-amino alcohols was conducted by ArCHAO-catalyzed enantioselective deamination and transaminase-catalyzed enantioselective amination to afford (S)-β-amino alcohols in excellent conversion (78–94 %) and enantiomeric excess (>99 %). Preparative-scale deracemization was carried out with 50 mM (6.859 g L?1) racemic 2-amino-2-phenylethanol, (S)-2-amino-2-phenylethanol was obtained in 75 % isolated yield and >99 % ee.
- Zhang, Jian-Dong,Chang, Ya-Wen,Dong, Rui,Yang, Xiao-Xiao,Gao, Li-Li,Li, Jing,Huang, Shuang-Ping,Guo, Xing-Mei,Zhang, Chao-Feng,Chang, Hong-Hong
-
p. 124 - 128
(2020/09/21)
-
- Catalytic enantioselective synthesis of β-amino alcohols by nitrene insertion
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Chiral β-amino alcohols are important building blocks for the synthesis of drugs, natural products, chiral auxiliaries, chiral ligands and chiral organocatalysts. The catalytic asymmetric β-amination of alcohols offers a direct strategy to access this class of molecules. Herein, we report a general intramolecular C(sp3)-H nitrene insertion method for the synthesis of chiral oxazolidin-2-ones as precursors of chiral β-amino alcohols. Specifically, the ring-closing C(sp3)-H amination of N-benzoyloxycarbamates with 2 mol% of a chiral ruthenium catalyst provides cyclic carbamates in up to 99% yield and with up to 99% ee. The method is applicable to benzylic, allylic, and propargylic C-H bonds and can even be applied to completely non-activated C (sp3)-H bonds, although with somewhat reduced yields and stereoselectivities. The obtained cyclic carbamates can subsequently be hydrolyzed to obtain chiral β-amino alcohols. The method is very practical as the catalyst can be easily synthesized on a gram scale and can be recycled after the reaction for further use. The synthetic value of the new method is demonstrated with the asymmetric synthesis of a chiral oxazolidin-2-one as intermediate for the synthesis of the natural product aurantioclavine and chiral β-amino alcohols that are intermediates for the synthesis of chiral amino acids, indane-derived chiral Box-ligands, and the natural products dihydrohamacanthin A and dragmacidin A.[Figure not available: see fulltext.].
- Zhou, Zijun,Tan, Yuqi,Shen, Xiang,Ivlev, Sergei,Meggers, Eric
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p. 452 - 458
(2020/12/31)
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- Site-Specific C(sp3)–H Aminations of Imidates and Amidines Enabled by Covalently Tethered Distonic Radical Anions
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The utilization of N-centered radicals to synthesize nitrogen-containing compounds has attracted considerable attention recently, due to their powerful reactivities and the concomitant construction of C?N bonds. However, the generation and control of N-centered radicals remain particularly challenging. We report a tethering strategy using SOMO-HOMO-converted distonic radical anions for the site-specific aminations of imidates and amidines with aid of the non-covalent interaction. This reaction features a remarkably broad substrate scope and also enables the late-stage functionalization of bioactive molecules. Furthermore, the reaction mechanism is thoroughly investigated through kinetic studies, Raman spectroscopy, electron paramagnetic resonance spectroscopy, and density functional theory calculations, revealing that the aminations likely involve direct homolytic cleavage of N?H bonds and subsequently controllable 1,5 or 1,6 hydrogen atom transfer.
- Fang, Yuanding,Fu, Kang,Shi, Lei,Zhao, Rong,Zhou, Jia
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p. 20682 - 20690
(2020/09/07)
-
- Visible-Light-Driven N-Heterocyclic Carbene Catalyzed γ- and ?-Alkylation with Alkyl Radicals
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The merging of photoredox catalysis and N-heterocyclic carbene (NHC) catalysis for γ- and ?-alkylation of enals with alkyl radicals was developed. The alkylation reaction of γ-oxidized enals with alkyl halides worked well for the synthesis γ-multisubstituted-α,β-unsaturated esters, including those with challenging vicinal all-carbon quaternary centers. The synthesis of ?-multisubstituted-α,β-γ,δ-diunsaturated esters by an unprecedented NHC-catalyzed ?-functionalization was also established.
- Dai, Lei,Xia, Zi-Hao,Gao, Yuan-Yuan,Gao, Zhong-Hua,Ye, Song
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p. 18124 - 18130
(2019/11/13)
-
- Catalytic β C-H amination: Via an imidate radical relay
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The first catalytic strategy to harness imidate radicals for C-H functionalization has been developed. This iodine-catalyzed approach enables β C-H amination of alcohols by an imidate-mediated radical relay. In contrast to our first-generation, (super)stoichiometric protocol, this catalytic method enables faster and more efficient reactivity. Furthermore, lower oxidant concentration affords broader functional group tolerance, including alkenes, alkynes, alcohols, carbonyls, and heteroarenes. Mechanistic experiments interrogating the electronic nature of the key 1,5 H-atom transfer event are included, as well as probes for chemo-, regio-, and stereo-selectivity.
- Stateman, Leah M.,Wappes, Ethan A.,Nakafuku, Kohki M.,Edwards, Kara M.,Nagib, David A.
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p. 2693 - 2699
(2019/03/06)
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- Highly Efficient and Robust Enantioselective Liquid–Liquid Extraction of 1,2-Amino Alcohols utilizing VAPOL- and VANOL-based Phosphoric Acid Hosts
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The large-scale production of enantiopure compounds in a cost-effective and environmentally friendly manner remains one of the major challenges of modern-day chemistry. The resolution of racemates through enantioselective liquid–liquid extraction was developed as a suitable solution but has remained largely underused, owing to a lack of highly efficient and robust chiral hosts to mediate the process. This paucity of hosts can in part be attributed to a poor understanding of the underlying principles behind these processes hindering the design of more efficient selectors. A previously untested class of hosts, VAPOL and VANOL derived phosphoric acids, has been studied in depth for the efficient enantioselective liquid–liquid extraction of 1,2-amino alcohols. A systematic investigation of extraction parameters was conducted, revealing many key interactions and DFT calculations illustrate the binding modes for the 1:1 complexes that are involved in chiral recognition. The resulting, now-optimized, procedures are highly robust and easy to implement. They are also easily scalable, as demonstrated by U-tube experiments.
- Pinxterhuis, Erik B.,Gualtierotti, Jean-Baptiste,Wezenberg, Sander J.,de Vries, Johannes G.,Feringa, Ben L.
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p. 178 - 184
(2017/12/15)
-
- Anti-HIV medicine containing indinavir and preparation method thereof
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The invention discloses anti-HIV medicine containing indinavir and a preparation method thereof. The anti-HIV medicine containing indinavir is prepared from indinavir and pharmaceutically acceptable carriers, wherein the chemical name of indinavir is (1(1S,2R),5(S))-2,3,5-tri-deoxy-N-(2,3-dihydro-2-hydroxyl-1H-indene-1-yl)-5-[2-[[(1,1-dimethyl ethyl) amino]carbonyl]-4-(3-picolyl)-1-piperazinyl]-2-(benzyl)-D-erythro-valeramide. The process of a preparation process is simple and compact; the raw materials can be easily obtained; economic performance and environment protection are realized; the industrialization can be favorably realized; the economic technology development of the indinavir raw medicine of the anti-HIV medicine can be promoted; the dissolving-out degree of the anti-HIV medicine containing indinavir is high; the effect is ideal; the medicine is suitable for mass production.
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- Radical-mediated intramolecular β-C(sp3)-H amidation of alkylimidates: Facile synthesis of 1,2-amino alcohols
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A new radical-mediated intramolecular β-C(sp3)-H amidation reaction of O-alkyl trichloro- or arylimidates is reported. Various oxazolines were efficiently prepared from easily accessible alcohol starting materials. The trichloro-oxazoline products can be hydrolyzed under mild conditions to give valuable 1,2-amino alcohols. This amidation reaction exhibits a broad substrate scope and good functional group tolerance, and offers a powerful means for the C(sp3)-H functionalization of alcohols. Mechanistic studies suggest that a sequence of 1,5-HAT of an imidate radical, iodination and cyclization might be operative.
- Mou, Xue-Qing,Chen, Xiang-Yu,Chen, Gong,He, Gang
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p. 515 - 518
(2018/01/19)
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- Directed β C-H Amination of Alcohols via Radical Relay Chaperones
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A radical-mediated strategy for β C-H amination of alcohols has been developed. This approach employs a radical relay chaperone, which serves as a traceless director that facilitates selective C-H functionalization via 1,5-hydrogen atom transfer (HAT) and enables net incorporation of ammonia at the β carbon of alcohols. The chaperones presented herein enable direct access to imidate radicals, allowing their first use for H atom abstraction. A streamlined protocol enables rapid conversion of alcohols to their β-amino analogs (via in situ conversion of alcohols to imidates, directed C-H amination, and hydrolysis to NH2). Mechanistic experiments indicate HAT is rate-limiting, whereas intramolecular amination is product- and stereo-determining.
- Wappes, Ethan A.,Nakafuku, Kohki M.,Nagib, David A.
-
p. 10204 - 10207
(2017/08/10)
-
- Diethylenetriamine-Mediated Direct Cleavage of Unactivated Carbamates and Ureas
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Diethylenetriamine is effective for the direct cleavage of unactivated carbamates and ureas without additional reagents and catalysts. Various carbamates and ureas were cleaved to afford products in good yield, and the reactions were not affected by air or moisture. Unique chemoselective cleavage of carbamate and urea in the presence of amides was also achieved.
- Noshita, Megumi,Shimizu, Yuhei,Morimoto, Hiroyuki,Ohshima, Takashi
-
supporting information
p. 6062 - 6065
(2016/12/09)
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- 3,3′-diaryl-BINOL phosphoric acids as enantioselective extractants of benzylic primary amines
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We report that 3,3′-diaryl-BINOL phosphoric acids are effective enantioselective extractants in chiral separation methods based on reactive liquid-liquid extraction. These new extractants are capable of separating racemic benzylic primary amine substrates. The effect of the nature of the substituents at the 3,3′-positions of the host were examined as well as the structure of the substrate, together with important parameters such as the organic solvent, the pH of the aqueous phase, and the host stoichiometry. Titration of the substrate with the host was monitored by FTIR, NMR, UV-Vis, and CD spectroscopy, which provided insight into the structure of the host-guest complex involved in extraction.
- Verkuijl, Bastiaan J.V.,De Vries, Johannes G.,Feringa, Ben L.
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experimental part
p. 34 - 43
(2011/10/08)
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- Cyclic trans-β-amino alcohols: Preparation and enzymatic kinetic resolution
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Enantioenriched cyclic β-amino alcohols, trans-2-aminocyclohexanols (ee, >99%), trans-2-aminocyclopentanols (ee, >99%), trans-1-amino-2- indanols (ee, >99%) and trans-2-amino-1-indanols (ee, ～98%) were prepared in high yields via an Arthrobacter sp. Lipase/PLAP catalyzed kinetic resolution of racemic phthalimido acetates. The addition of toluene as a co-solvent dramatically improved the hydrolysis and enantioselectivity, whereas for indanols, substrate immobilization on Celite improved the efficacy of the kinetic resolution.
- Rouf, Abdul,Gupta, Pankaj,Aga, Mushtaq A.,Kumar, Brijesh,Parshad, Rajinder,Taneja, Subhash C.
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scheme or table
p. 2134 - 2143
(2012/05/04)
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- COMPOSITIONS AND METHODS FOR CYCLOFRUCTANS AS SEPARATION AGENTS
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The present invention relates to derivatized cyclofructan compounds, compositions comprising derivatized cyclofructan compounds, and methods of using compositions comprising derivatized cyclofructan compounds for chromatographic separations of chemical species, including enantiomers. Said compositions may comprise a solid support and/or polymers comprising derivatized cyclofructan compounds.
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Page/Page column 45-49; 53
(2010/12/31)
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- Development of new HPLC chiral stationary phases based on native and derivatized cyclofructans
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An unusual class of chiral selectors, cyclofructans, is introduced for the first time as bonded chiral stationary phases. Compared to native cyclofructans (CFs), which have rather limited capabilities as chiral selectors, aliphatic-and aromatic-functionalized CF6s possess unique and very different enantiomeric selectivities. Indeed, they are shown to separate a very broad range of racemic compounds. In particular, aliphatic-derivatized CF6s with a low substitution degree baseline separate all tested chiral primary amines. It appears that partial derivatization on the CF6 molecule disrupts the molecular internal hydrogen bonding, thereby making the core of the molecule more accessible. In contrast, highly aromaticfunctionalized CF6 stationary phases lose most of the enantioselective capabilities toward primary amines, however they gain broad selectivity for most other types of analytes. This class of stationary phases also demonstrates high "loadability" and therefore has great potential for preparative separations. The variations in enantiomeric selectivity often can be correlated with distinct structural features of the selector. The separations occur predominantly in the presence of organic solvents.
- Sun, Ping,Wang, Chunlei,Breitbach, Zachary S.,Zhang, Ying,Armstrong, Daniel W.
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experimental part
p. 10215 - 10226
(2010/05/01)
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- Aryl sulfonamido indane inhibitors of the Kv1.5 ion channel
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A collection of aryl sulfonamido indanes based on the lead compound 1 was synthesized and evaluated for Kv1.5 inhibitory activity. Kv1.5 inhibitors have the potential to be atrium-selective agents for treatment of atrial fibrillation. (1R,2R)-1 has an IC50 of 0.033 μM against Kv1.5 and is selective against other cardiac ion channels, including hERG.
- Gross, Michael F.,Beaudoin, Serge,McNaughton-Smith, Grant,Amato, George S.,Castle, Neil A.,Huang, Christine,Zou, Anruo,Yu, Weifeng
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p. 2849 - 2853
(2008/02/11)
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- Convenient and inexpensive synthesis of (1R,2R)-trans-1-amino-6-nitroindan- 2-ol
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Racemic trans-1-amino-6-nitroindam-2-ol (rac-1) has been prepared in five steps from inexpensive indene (7) in 96% overall yield. The key step was a direct nitration of the known trans-1-aminoindan-2-ol (rac-9) which gave sulfuric acid mono-(rac-trans-1-amino-6-nitroindan-2-yl) ester (rac-10) in quantitative yield. The latter was quantitatively converted into rac-1 by treatment with aqueous 6 N HCl and then ammonia solutions. The same transformations of (1R,2R)-9 [prepared by deracemization of rac-9 with (-)-dibenzoyl-L-tartaric acid (DBT)] proceeded without loss of the optical activity. Deracemization of rac-1 applying (+)-(5)-L-mandelic acid (MA) furnished (1R,2R)-1 and (1s,2s)-1 in 34 and 17% yield, respectively, with e.e. ≥ 98 and 97.6%, respectively. Procedures for recycling of the chiral auxiliaries DBT and MA are also described. The structures of key intermediates were confirmed by X-ray crystal structure analysis.
- Kozhushkov, Sergei I.,Yufit, Dmitrii S.,De Meijere, Armin
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p. 255 - 265
(2007/10/03)
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- Chemically modified mutant serine hydrolases show improved catalytic activity and chiral selectivity
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This invention provides novel chemically modified mutant serine hydrolases that catalyze a transamidation and/or a transpeptidation and/or a transesterification reaction. The modified serine hydrolases have one or more amino acid residues in a subsite replaced with a cysteine, wherein the cysteine is modified by replacing the thiol hydrogen in the cysteine with a substituent group providing a thiol side chain comprising a moiety selected from the group consisting of a polar aromatic substituent, an alkyl amino group with a positive charge, and a glycoside. In particularly preferred embodiments, the substitutents include an oxazolidinone, a C1 to C15 alkyl amino group with a positive charge, or a glycoside.
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- Resolution of racemic cis-1-amino-2-indanol by diastereomeric salt formation with (S)-2-phenylpropionic acid
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Resolution of racemic cis-1-amino-2-indanol 1, a key intermediate for the synthesis of indinavir, is reported. The conditions were optimized for an industrial-scale resolution of racemic cis-1 using (S)-2-phenylpropionic acid 6 as the resolving agent and ethanol as the solvent. The less-soluble diastereomeric salt, (1R,2S)-1·(S)-6, was obtained in 35% yield with 99% de (E >69%) by crystallization. Resolving agent 6 was efficiently recovered from the salt and the mother liquor.
- Sakurai, Rumiko,Sakai, Kenichi
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p. 411 - 413
(2007/10/03)
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- Asymmetric transfer hydrogenation of ketones using amino alcohol and monotosylated diamine derivatives of indane
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A series of 1,2-amino alcohol and 1,2-monotosylated diamine derivatives of indane have been applied as ligands in the asymmetric ruthenium(II)-catalysed transfer hydrogenation reaction of a series of ketones. Of these, the cis-1-aminoindan-2-ol derivative gives some of the highest asymmetric inductions reported for any amino alcohol ligand in this application.
- Palmer, Matthew J.,Kenny, Jennifer A.,Walsgrove, Tim,Kawamoto, Aparecida M.,Wills, Martin
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p. 416 - 427
(2007/10/03)
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- PREPARATION OF HYDROXY COMPOUNDS BY BIOCONVERSION WITH DIOXYGENASE
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PCT No. PCT/GB96/01208 Sec. 371 Date Nov. 21, 1997 Sec. 102(e) Date Nov. 21, 1997 PCT Filed May 20, 1996 PCT Pub. No. WO96/37628 PCT Pub. Date Nov. 28, 1996A process for preparing a compound of Formula (3) in which R2 is -H; which comprises the steps: i) conversion of a compound of Formula (1) into a compound of Formula (2) using a dioxygenase enzyme; ii) conversion of the compound of Formula (2) into a compound of Formula (3) wherein is -COR; and iii) conversion of the compound of Formula (3) in which R2 is -COR into a compound of Formula (3) in which R2 is -H; wherein R2, a, b, c, d, Z, m and X are as defined in claim 1. Also claimed are individual steps of the process and new compounds of Formula (2).
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- Process for the separation of a mixture of enantiomers
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A diastereomer complex obtained via a process for the separation of enantiomers is disclosed, wherein separation can be rapidly effected such that enantiomers are obtained with high e.e. values. The process pets the separation of mixtures of enantiomers in which more than one resolving agent is used, of which at least one resolving agent is optically active, and which yields a diastereomer complex containing at least two resolving agents in optically active form. The process provides for, inter alia, a diastereomer complex having at least three compounds of which at least two compounds are resolving agents in optically active form, and at least one compound is an onantiomer in optically active form. Also provided is a diastereomer complex having at least three compounds of which at lea one compound is a resolving agent in optically active form, and at least two compounds which are enantiomers in optically active form.
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- Lipase-mediated kinetic resolution of cis-1,2-indandiol and the Ritter reaction of its mono-acetate
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Lipase-mediated kinetic resolution of cis-1,2-indandiol 5 in the presence of lipase PS was examined. Enantiomerically enriched (1S,2R)-2-acetoxy-1-indanol 6a was obtained when cis-1,2-indandiol 5 was treated with one equivalent of vinyl acetate. Treatment of 5 with two equivalents of vinyl acetate furnished a mixture of (1R,2S)-2-acetoxy-1-indanol 6a and (1R,2S)-1-acetoxy-2-indanol 6b. A route to both enantiomers of 1 was also developed by using the enantiomerically enriched mono-acetate thus obtained.
- Nakano, Shigeru,Igarashi, Yoshio,Nohira, Hiroyuki
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- Kinetic resolution of amino alcohol derivatives with a chiral nucleophilic catalyst: Access to enantiopure cyclic cis-amino alcohols
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Acylative kinetic resolution of racemic cyclic cis-amino alcohol derivatives with a chiral nucleophilic catalyst proceeds enantioselectively (s = 10-21) at ambient temperature to give enantiopure recovered materials, and the % conversion of the acylation can be readily controlled by the amount of acid anhydride.
- Kawabata,Yamamoto,Momose,Yoshida,Nagaoka,Fuji
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p. 2700 - 2701
(2007/10/03)
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- Process for preparing 4-tert-butyloxycarbonyl-(S)-piperazine-2-tert-butylcarboxamide
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An improved process using chiral hydrogenation is described for the synthesis in high yields of a 4-protected-(S)-piperazine-2-tert-butylcarboxamide, an intermediate for an HIV protease inhibitor.
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- Oxazolidinone compounds and process for the preparation thereof
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The present invention produces novel cis-oxazolidinone compound which is racemic form or optically active form, of a formula (1) STR1 wherein R represents C1 -C6 alkyl group, C2 -C6 alkenyl group, C1 -C6 alkoxyl group, C1 -C6 alkylamino group, aryl group or halogen atom, and oxazolidinone ring is at cis-configuration, comprising reacting cis-1,2-indene epoxide of a formula (3) STR2 form, with sulfonyl isocyanate compound of a formula (4) STR3 in the presence of metal halide catalyst. Further, cis-1-amino-2-indanol is produced by hydrolyzing the oxazolidinone compound. The latter compound is useful as an intermediate of HIV-drug.
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- Process for preparing indan derivatives
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This invention relates to a process for preparing indan derivatives and comprises a process for preparing cis-1-amino-2-indanol by treating (±)indan-1,2-diol and/or its 2-formate derivative with specific microbes to give optically active 2-hydroxy-1-indanone, converting the optically active 2-hydroxy-1-indanone to its oxime, and treating the oxime with hydrogen or a hydrogen donor in the presence of a heterogeneous hydrogenation catalyst, a process for preparing optically active 2-hydroxy-1-indanone and/or optically active indan-1,2-diol by treating (±)indan-1,2-diol and/or its 2-formate derivative with specific microbes, and a process for preparing cis-1-amino-2-indanol by treating the oxime of 2-hydroxy-1-indanone with hydrogen or a hydrogen donor in the presence of a heterogeneous hydrogenation catalyst.
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- Chiral bisphosphines
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New chiral biphosphines, e.g., STR1 are useful as key components in catalysts for asymmetric reactions, providing desirably high enantiomeric excess (ee).
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- PROCESS FOR PREPARING 4-TERT-BUTYLOXYCARBONYL-(S)-PIPERAZINE-2-TERT-BUTYLCARBOXAMIDE
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An improved process using chiral hydrogenation is described for the synthesis in high yields of a 4-protected-(S)-piperazine-2-tert-butylcarboxaimide, an intermediate for an HIV protease inhibitor.
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- Precursors for the production of chiral vicinal aminoalcohols
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The disclosure describes new compositions of matter useful for the preparation of optically-active vicinal aminoalcohols. The compositions are chiral β-hydroxycarboxamides, β-hydroxyhydraxides, and β-hydroxyhydroxamic acids.
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- Efficient synthesis of a chiral mediator
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An efficient method for the quantitative preparation and isolation of a compound of formula I STR1 or its enantiomer, a chiral mediator used in enantioselective synthesis.
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- A practical synthesis of (1S,2R)-1-amino-2-indanol, a key component of an HIV protease inhibitor, indinavir
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A synthesis of (1S,2R)-1-amino-2-indanol (1), a key component of an HIV protease inhibitor, was accomplished through (R)-2-hydroxy-1-indanone ((R)- 3), which was prepared by an intramolecular Friedel-Crafts acylation of (R)2- acetoxy-3-phenylpropanoic acid readily available from D-(R)-phenylalanine. Alternatively, (R)-3 was obtained by an enzymatic resolution of (±)-2- acetoxy-1-indanone. Ketone (R)-3 was convened into 1 through an oxime formation and diastereoselective hydrogenation.
- Kajiro, Hiroshi,Mitamura, Shuichi,Mori, Atsunori,Hiyama, Tamejiro
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p. 1093 - 1100
(2007/10/03)
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- Manganese catalyzed asymmetric oxidation of alkanes to optically active ketones bearing asymmetric center at the α- position
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Chiral (salen)manganese(III) complex catalyzed oxidation of symmetrical alkanes with iodosylbenzene gives the corresponding optically active ketones (up to 70% ee). The optically active 2-hydroxy-1-indanone (7) thus obtained is a versatile precursor of cis-1-amino-2-indanol (8) which is a key intermediate of chiral auxiliary and anti HIV protease inhibitor (9).
- Komiya, Naruyoshi,Noji, Satoru,Murahashi, Shun-Ichi
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p. 7921 - 7924
(2007/10/03)
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- PROCESS FOR PREPARING 4-TERT-BUTYLOXYCARBONYL-(S)-PIPERAZINE-2-TERT-BUTYLCARBOXAMIDE
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An improved process using chiral hydrogenation is described for the synthesis in high yields of a 4-protected-(S)-piperazine-2-tert-butyl-carboxamide, an intermediate for an HIV protease inhibitor.
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- A general chemoenzymatic synthesis of enenatiopures cis β-amino alcohols from microbially derived cis-glycols
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Enantiomerically pure cis-glycols, derived through the microbial metabolism of hydrocarbons, represent a valuable chiral pool for the synthesis of cis β-amino alcohols. One generally applicable route to these important chiral intermediates is described. Reaction of the metabolically formed diol with α-acetoxyisobutyryl chloride affords regio- and stereoselectively a single trans-1,2-chlorohydrin acetate isomer. Displacement of chloride by azide, aminolysis of the ester and reduction of the azide provides the requisite amino alcohols. This 4-step route is highly efficient and affords the cis β-amino alcohol enantiomers in 41-57% overall yields. Using the highly enantiopure amino alcohols diastereomeric oxazaborolidines were prepared with both (-)-(S)- and (+)-(R)-[2-(1-methoxyethyl)phenyl]boronic acids. As described herein, these derivatives are potentially useful for absolute configurational assignments to cis amino alcohols.
- Lakshman, Mahesh K.,Chaturvedi, Surendrakumar,Zajc, Barbara,Gibson, David T.,Resnick, Sol M.
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p. 1352 - 1356
(2007/10/03)
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- Method of producing cis-1-aminoindan-2-ol
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1,2-di-substituted indan expressed by general formula (I) wherein X is a substituent which can be drawn out under an acidic condition to form a carbocation at 1-position of an indan skeleton, Y is a halogen atom, and X and Y can be in either cis- or trans-configuration forming either a racemic body or an optically active substance; or 1,2-di-substituted indan expressed by general formula (I') wherein X is a substituent which can be drawn out under an acidic condition to form a carbocation at 1-position of an indan skeleton, and X and OH group can be in either cis- or trans-configuration forming either a racemic body or an optically-active substance; or cis-1,2-epoxyindan expressed by general formula (VI) wherein R is phenyl or a lower alkyl group, oxazoline ring is in cis-configuration forming either a racemic body or an optically active substance is reacted, under an acidic condition, with a nitrile expressed by general formula (II) wherein R is phenyl or a lower alkyl group to produce cis-1-aminoindan-2-ol expressed by general formula (V) wherein NH2 and OH groups are in cis-configuration forming either a racemic body or an optically-active substance. STR1
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- Process to make HIV protease inhibitor from (2S)-4-picolyl-2-piperazine-t-butylcarboxamide
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A process for making a clinically efficacious HIV protease inhibitor eliminates one step in its synthesis, by an alternative convergent synthesis using 2(S)-4-picolyl-2-piperazine-t-butylcarboxamide as an intermediate.
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- Process for making HIV protease inhibitors
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A process for making a clinically efficacious HIV protease inhibitor Compound J eliminates one step in its synthesis, by an improved, alternative synthesis of the 2(S)-4-picolyl-2-piperazine-t-butyl-carboxamide intermediate.
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- Optically pure 1-amido-2-indanols
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A two-step process for the conversion of a trans-1-amino-2-hydroxycycloalkane stereoselectively to a cis-1-amino-2-hydroxycycloalkane is disclosed. The novel step, a one-step hydrolysis with formal inversion, can be used to convert an amide of a trans-1-amino-2-hydroxycycloalkane to a cis-1-amino-2-hydroxycycloalkane. Methods for obtaining the trans-1-amino-2-hydroxycycloalkanes and their amides from alkenes are also disclosed. Novel, optically active 1-amido-2-indanols and 1-amino-2-alkanols are also disclosed.
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- Optically pure 1-amino-2-indanols
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A two-step process for the conversion of a trans-1-amino-2-hydroxycycloalkane stereoselectively to a cis-1-amino-2-hydroxycycloalkane is disclosed. The novel step, a one-step hydrolysis with formal inversion, can be used to convert an amide of a trans-1-amino-2-hydroxycycloalkane to a cis-1-amino-2-hydroxycycloalkane. Methods for obtaining the trans-1-amino-2-hydroxycycloalkanes and their amides from alkenes are also disclosed, as are the novel, substantially optically pure 1-amino-2-indanols and 1-amido-2-indanols obtained thereby. A preferred process converts indene to cis-1-amino-2-indanol.
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- A convenient enzymatic route to optically active 1-aminoindan-2-ol: Versatile ligands for HIV-1 protease inhibitors and asymmetric syntheses
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(1S,2R)- and (1R,2S)-1-aminoindan-2-ol were prepared in high enantiomeric excess (> 96%) by an immobilized lipase-catalyzed selective acylation of racemic trans-1-azidoindan-2-ol.
- Ghosh, Arun K.,Kincaid, John F.,Haske, Michael G.
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p. 541 - 544
(2007/10/03)
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- Regio and stereocontrolled synthesis of aryl cis aminoalcohols from cis glycols
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Reaction of aryl substituted cis diols with α-acetoxyisobutyryl chloride results in the formation of trans vicinal chlorohydrin acetates where the halide is benzylic. Displacement of chloride with azide ion, deprotection of the ester and reduction of the azide furnishes the requisite cis aminoalcohols. This facile four-step procedure results in the exclusive replacement of a benzylic hydroxyl with an amino group, with a net retention of stereochemistry. This set of transformations is generally applicable to a wide variety of cis diols, and the overall yields are excellent.
- Lakshman, Mahesh K.,Zajc, Barbara
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p. 2529 - 2532
(2007/10/03)
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- Stereoselective dioxygenase-catalysed benzylic hydroxylation at prochiral methylene groups in the chemoenzymatic synthesis of enantiopure vicinal aminoindanols
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Enantiopure benzylic alcohols containing two stereogenic centres in a cis- relationship result from stereoselective monohydroxylation of achiral 2- substituted indans in cultures of Pseudomonas putida UV4 and are used in the chemoenzymatic synthesis of both cis- and trans-aminoindanol enantiomers.
- Boyd, Derek R.,Sharma, Narain D.,Bowers, Nigel I.,Goodrich, Peter A.,Groocock, Melanie R.,Blacker, A.John,Clarke, David A.,Howard, Tina,Dalton, Howard
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p. 1559 - 1562
(2007/10/03)
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- Inhibitors of human immunodeficiency virus type 1 protease containing 2- aminobenzyl-substituted 4-amino-3-hydroxy-5-phenylpentanoic acid: Synthesis, activity, and oral bioavailability
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Systematic modifications of HIV protease inhibitor (2R,3S,4S)-4- [[(benzyloxycarbonyl)-L-valyl]amino]-3-hydroxy-2-[(4-methoxybenzyl)amino]-5- (phenylpentanoyl)-L-valine 2-(aminomethyl)-benzimidazole amide led to a novel series of inhibitors with a shortened, modified carboxy terminus. Their synthesis, in vitro enzyme inhibitory data, and antiviral activities are reported. Of particular interest are derivatives featuring the (1S,2R)-1- amino-2-hydroxyindan moiety at the P2'-position since some of them exhibit substantial oral bioavailability in mice. The influence of aqueous solubility and structural parameters on the oral resorption of the inhibitors is discussed. Optimum enhancement of oral bioavailability was observed with L- tert-leucine in P2-position, resulting in the discovery of (2R,3S,4S)-4- [[(benzyloxycarbonyl)-L-tert-leucyl]amino]-3-hydroxy-2-[(4- methoxybenzyl)amino]-5-phenylpentanoic acid (1S,2R)-1-amino-2-hydroxyindan amide which combines high antiviral activity (IC50 = 250 nM) with a good pharmacokinetic profile (AUC = 82.5 μM · h at a dose of 125 mg/kg po in mice).
- Lehr,Billich,Charpiot,Ettmayer,Scholz,Rosenwirth,Gstach
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p. 2060 - 2067
(2007/10/03)
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- Synthesis and protein kinase C inhibitory activities of indane analogs of balanol
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Regio- and stereoisomeric indane analogs (4-6) of balanol (-)-1, a potent protein kinase C (PKC) inhibitor, were synthesized in which the perhydroazepine of balanol was replaced by an indane nucleus. Analog (-)-4 and its racemic regioisomer 6 were found to have highly potent PKC inhibitory activities. In addition, compound (-)-4 displayed excellent kinase selectivity for PKC over PKA.
- Hu, Hong,Hollinshead, Sean P.,Hall, Steven E.,Kalter, Kiyomi,Ballas, Lawrence M.
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p. 973 - 978
(2007/10/03)
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- Reductive amination process
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A process of reductive amination efficiently yields an HIV protease inhibitor.
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- Process for preparing cyclic CIS-1-amino-2-alkanols
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A two-step process for the conversion of a trans-1-amino-2-hydroxycycloalkane stereoselectively to a cis-1-amino-2-hydroxycycloalkane is disclosed. The novel step, a one-step hydrolysis with formal inversion, can be used to convert an amide of a trans-1-amino-2-hydroxycycloalkane to a cis-1-amino-2-hydroxycycloalkane. Methods for obtaining the trans-1-amino-2-hydroxycycloalkanes and their amides from alkenes are also disclosed. A preferred process converts indene to cis-1-amino-2-indanol.
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- Tetrahydroindeno[1,2-D][1,3,2]oxazaboroles and their use as enantioselective catalysts
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A method for the enantioselective reduction of prochiral ketones using catalytic amounts of tetrahydroindeno[1,2-d][1,3,2] oxazaboroles of formula II is disclosed. STR1 The oxazaboroles can be generated in situ from the corresponding cis-1-amino-2-indanols or imino indanols (III) STR2 Novel compounds of formulas II and III are also disclosed.
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