Amino Diol Research Articles

Complementary Stereocontrolled Approaches to 2-Pyrrolidinones Bearing a Vicinal Amino Diol Subunit with Three Continuous Chiral Centers: A Formal Asymmetric Synthesis of (−)-Detoxinine

We report herein two stereocomplementary approaches to erythro/trans and threo/cis vicinal amino diol subunits containing 2-pyrrolidinones (9 and 10) starting from the known enamides 7, easily available from malimides. The first approach consists of an epoxidation-reductive dehydroxylation procedure, and the second one is based on hydroboration-oxidation reactions. Using the second method, a formal asymmetric synthesis of (-)-detoxinine was achieved.

Stereoselective construction of the 1,1,1-trifluoroisopropyl moiety by asymmetric hydrogenation of 2-(trifluoromethyl)allylic alcohols and its application to the synthesis of a trifluoromethylated amino diol

The asymmetric hydrogenation of a series of 2-(trifluoromethyl)allylic alcohols 1a– g catalyzed by a BINAP–Ru(II) diacetate complex gave the corresponding products 2a– g in high yield (>90% yield) and high diastereoselectivity (>95% de). The asymmetric hydrogenation of 2-(trifluoromethyl)allylic alcohols provided an efficient stereoselective method to construct the 1,1,1-trifluoroisopropyl moiety. Based on the asymmetric hydrogenation of the 2-(trifluoromethyl)allylic alcohol 5a prepared by the reaction of ( R)-2,2-dimethyl-1,3-dioxolane-4-carboxaldehyde with 3,3,3-trifluoroisopropenyllithium, (2 R,3 S,4 R)-4-trifluoromethyl-1-aminopentane-2,3-diol 9 was synthesized in 36% overall yield over five steps.

Synthesis of Symmetrical and Unsymmetrical Pyrazines.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Synthesis of the dysiherbaine tetrahydropyran core employing a tethered aminohydroxylation reaction

A stereocontrolled and scalable synthesis of an advanced intermediate of the dysiherbaine tetrahydropyran core has been achieved in 11 steps and 27% overall yield. The key feature of this synthetic approach is the application of the Donohoe tethered aminohydroxylation reaction to install the amino diol and establish the four contiguous syn stereocenters on the tetrahydropyran ring.

Synthesis of symmetrical and unsymmetrical pyrazines.

Opening of representative epoxides with 1,2-amino alcohols delivered the amino diols. The product amino diols were then oxidized under Swern conditions. The amino diketones so prepared were not isolated, but were condensed directly with hydroxylamine to give the substituted pyrazines.

Diastereo- and Enantioselective Synthesis of Nitroso Diels−Alder-Type Bicycloketones Using Dienamine: Mechanistic Insight into Sequential Nitroso Aldol/Michael Reaction and Application for Optically Pure 1-Amino-3,4-diol Synthesis

This article presents complete diastereo- and highly enantioselective synthesis of nitroso Diels-Alder-type bicycloketones using dienamine. With the hydrogen bonding of two hydroxyls in the bulky binaphthol 1c, high enantioselectivities and complete diastereoselectivity are realized in 2-oxa-3-aza-bicycloketone synthesis. On the other hand, alpha,beta-unsaturated ketone can be employed as diene precursor, utilizing readily available tetrazole catalyst 3b, to provide the 3-oxa-2-aza-bicycloketones in moderate yields with complete enantioselectivities. Investigation into the reaction utilizing 2-morpholino-4,4-diphenylcyclohexadiene 2d clearly indicated that cyclization with the bulky binaphthol 1c is involved in the sequential process, the N-nitroso aldol reaction, followed by Michael addition. In addition, optically pure 1-amino-3,4-diol is synthesized from 2-oxa-3-aza-bicycloketones. Use of p-phenoxynitrosobenzene allows access to protected amino diol via cleavage of the N-Ph bond.

Stereocontrolled Transformations of trans α,β‐Aziridine Aldehydes Toward Different Amino Hydroxylated Structures.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Stereocontrolled Transformations of trans α,β‐Aziridine Aldehydes toward Different Amino Hydroxylated Structures

The stereocontrolled condensation of methyl ketones to trans α,β‐aziridine aldehydes creates functionalized aldols, valuable precursors for different amino hydroxylated structures, such as amino alcohols, amino diols, α‐tetrahydrofuryl amides, and α‐furyl amides.

Regioselective and Diastereoselective Amination with Use of Chlorosulfonyl Isocyanate: A Short and Efficient Synthesis of (−)-Cytoxazone

The total synthesis of (-)-cytoxazone 1 was achieved in six linear steps (34% overall yield) from p-anisaldehyde. The key steps in this route are the regioselective and stereoselective introduction of a N-protected amine group, using the CSI reaction of the anti-1,2-dimethyl ether 3, and the subsequent regioselective cyclization of the N-protected amino diol 13 to give the 2-oxazolidinone unit of (-)-cytoxazone 1. [reaction: see text]

Synthesis and application of L-N-Boc-N-methyl-β-hydroxyvaline in the preparation of a depsipeptide

Enantiopure (>99% ee) L-N-tert-butyloxycarbonyl-N-methyl-β-hydroxyvaline (2) was synthesized in six steps and 43% overall yield from D-serine methyl ester (5). Methyl (4S)-N-(9-phenylfluoren-9-yl)-oxazolidine-4-carboxylate (7) was prepared in two steps and 73% yield by N-phenylfluorenation of 5 followed by cyclization of N-(PhF)amino alcohol 6 with formaldehyde and catalytic p-toluenesulfonic acid (PhF = 9-phenylfluoren-9-yl). The addition of MeLi to oxazolidine carboxylate 7 produced the tertiary alcohol 8 in 91% yield. Oxazolidines 8 equilibrated with oxazolidine 9 under acidic conditions. Reduction of pure 8 or the mixture of oxazolidines 8 and 9 with NaCNBH3 and hydrochloric acid in anhydrous dioxane afforded N-methyl amino diol 11 in 86%–92% yields. Attempts to selectively oxidize N-(PhF)amino diol 11 were unsuccessful; however, hydrogenation of 11 in the presence of di-tert-butyl dicarbonate gave the corresponding N-(Boc)amino diol 12 in 82% yield. Selective oxidation of diol 12 was performed using a cocktail containing TEMPO free radical, NaClO2, and NaOCl to give L-N-Boc-N-methyl-β-hydroxyvaline (2) in 87% yield. Coupling of β-hydroxyvaline 2 and (S)-2-hydroxy-3-methylbutanoate (15) was accomplished by using the methodology of Mitsunobu to provide depsipeptide Boc-(S)-HOMeVal-(R)-Hmb (4) for use as a building block in the synthesis of the cyclic antifungal depsipeptide aureobasidin B.Key words: N-methylated amino acid, serine, depsipeptide, aureobasidin.

Synthetic Studies toward Ecteinascidin 743

An efficient synthesis of a fully functionalized tetracycle (A-B-C-H) 7 containing a 1,4-bridged 10-membered lactone was developed. Phenolic aldol condensation between 2-methylsesamol (15) and Garner's aldehyde provided the protected amino diol 16, which was converted to free amine 11 in excellent yield. A Pictet-Spengler reaction between 11 and ethyl glyoxylate under carefully controlled conditions (LiCl, toluene, 1,1,1,3,3,3-hexafluoro-2-propanol, room temperature) provided the acid-sensitive tetrahydroisoquinoline (18) in high yield, which was converted to the amino alcohol 9. Enantioselective alkylation of a glycine template in the presence of a catalytic amount of chiral cinchonidium salt was the key step for the access of enantiomerically pure amino aldehyde 10. Union of the two fragments 9 and 10 via oxazolidine intermediate afforded amino nitrile 39, which upon esterification of the primary alcohol with (R)-N-(S-4,4',4' '-trimethoxyltrityl) Cys (42) afforded 43. Cyclization of 43 (1% trifluoroacetic acid in trifluoroethanol) provided compound 44 by a domino process involving (a) unmasking of the S-trimethoxytrityl group, (b) fragmentation of dioxane assisted by an electron-rich aromatic ring, and (c) formation of a 1,4-bridged 10-membered lactone via formation of a sulfide linkage. Treatment of 7, obtained in two steps from 44b, under acidic conditions (0.5% methyl sulfonic acid in acetonitrile) afforded the pentacyclic compound 51 via fragmentation of the 10-membered cyclic sulfide followed by an intramolecular Pictet-Spengler reaction.

Synthesis of Enantiopure Functionalized β-Alkoxy γ-Amino Aldehydes by a New Internal Redox Ring Cleavage of Carbohydrate-Derived 1,2-Oxazines

N-Methylation of 3,6-dihydro-2H-1,2-oxazines such as syn-1 or anti-1 followed by treatment with triethylamine smoothly furnished enantiopure β-alkoxy γ-amino aldehydes syn-2 and anti-2 in excellent yields. This mild N-O bond cleavage may be classified as internal redox process. Similar transformations of related 1,2-oxazines led to the expected compound anti-6 or to protected 4-amino hexose derivative 10. Starting from syn-2 or anti-2 condensation with hydrazine afforded new pyrazole derivatives syn-11 and anti-11 with stereodefined and protected amino diol side chain. ­Heterocycles syn- 12 and syn-13 were prepared from syn-2 by condensation with 2-aminoimidazole or 2-aminobenzimidazole, respectively.

Efficient, Stereoselective Synthesis of trans‐2,5‐Disubstituted Morpholines.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Oxidation of Amino Diols Mediated by Homogeneous and Heterogeneous TEMPO

AbstractThe conversion of amino diols to aminohydroxy acids by oxidation of the primary hydroxy group mediated by homogeneous and heterogeneous TEMPO (2,2,6,6‐tetramethylpiperidine 1‐oxyl radical) is reported. The synthesis uses NaOCl as primary oxidant and TEMPO, either dissolved in the homogeneous phase or entrapped in a sol‐gel matrix, as catalytic mediator. Homogeneous TEMPO is suitable for the oxidation of aliphatic methylamino diols, while the hybrid organic‐inorganic silica sol‐gel catalysts are more selective mediators for the oxidation of benzylic amino diols like the potent antibiotic chloramphenicol which, under homogeneous conditions, are unselectively oxidized to benzoic acids.

Synthetic Studies on Ecteinascidin 743: Rapid Access to the Fully Functionalized Tetrahydroisoquinoline with a Bridged 10‐Membered Sulfur Containing Macrocycle.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Efficient, stereoselective synthesis of trans-2,5-disubstituted morpholines.

[reaction: see text] Enantio- and diastereoselective syntheses of trans-2,5-disubstituted morpholine derivatives are described. The routes are initiated by the reaction of enantiopure epoxides (2) with amino alcohols (3) and address the problem of regioselective hydroxyl activation-ring closure of the resulting amino diol adducts for (amino alcohol-derived) alkyl substituents of different steric demands.

Studies Towards the Synthesis of Superstolide A: An Aldol-Based Construction of an Advanced C1-C5/C20-C26 Segment

Based on a boron-mediated syn aldol reaction of an alanine-derived ethyl ketone with an α-chiral aldehyde partner, an advanced intermediate for superstolide A was assembled in a highly stereocontrolled fashion. Controlled 1,3-anti reduction of the resulting β-hydroxy ketone gave the characteristic amino diol stereopentad of superstolide, followed by a Takai olefination and esterification of the C23 hydroxyl to provide the elaborated C1-C5/C20-C26 segment 3.

A Short Synthesis of (-)-Deoxoprosophylline

Syntheses of (-)-deoxoprosophylline from chiral L-N,N-di(benzyl)serine (TBDMS) aldehyde is reported. A highly diastereoselective nucleophilic addn. of Buechi's Grignard reagent to chiral serinal followed by an intramol. reductive amination of w-oxo amino diol are two key steps of the present synthesis. The target compd. was (2S,3R,6R)-6-dodecyl-3-hydroxy-2-piperidinemethanol, which is related to the Prosopis africana piperidine alkaloid family. [on SciFinder (R)]

Addendum to “Nucleophilic fluorination of amino alcohols and diols using Deoxofluor” [J. Fluorine Chem. 116 (2002) 23–26

Addendum to “Nucleophilic fluorination of amino alcohols and diols using Deoxofluor” [J. Fluorine Chem. 116 (2002) 23–26

Formation and characterization of a multicomponent equilibrium system derived from cis- and trans-1-aminomethylcyclohexane-1,2-diol.

Both cis and trans isomers of amino diols 3-6 were prepared stereoselectively. In the reactions between 3-6 and phenyl isothiocyanate, the ring closure proceeded regioselectively and resulted only in spiro derivatives of 2-phenyliminooxazolidines 9, 10, 13, and 14. The reaction of cis- (or trans-)1-aminomethylcyclohexane-1,2-diol 4 (or 6) with 1 equiv of an aromatic aldehyde 15a-g in EtOH at room temperature resulted in a complex, multicomponent equilibrium mixture of 16a-g and 18a-g (or 17a-g and 19a-g), in each case consisting of a five-component, ring-chain tautomeric system 16A-E (or 17A-E), involving the Schiff base, two epimeric spirooxazolidines, two epimeric condensed 1,3-oxazines, and some of the four tricyclic compounds 18A-D (or 19A-D). The five-component, ring-chain equilibria were found to be adequately described by the Hammett-Brown linear free energy equation.