Ns strategies: a highly versatile synthetic method for amines

Kan, Toshiyuki; Fukuyama, Tohru

doi:10.1039/b311203a

Cited by 498 publications

(361 citation statements)

References 31 publications

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“…In order to demonstrate that our catalytic system is suitable for use with alcohol substrates other than benzylic alcohols, hexen-1-ol, isobutyl alcohol, and 1-adamantanol were subjected to the reaction conditions with para-toluenesulfonamide (2). Satisfactorily, all three alcohols afforded the corresponding sulfonamide products 7a, 7b, and 7c with 76, 47, and 87 % yield, respectively.…”

Section: Resultsmentioning

confidence: 99%

Direct Sulfonamidation of Primary and Secondary Benzylic Alcohols Catalyzed by a Boronic Acid/Oxalic Acid System

2017

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Section: Resultsmentioning

confidence: 99%

Direct Sulfonamidation of Primary and Secondary Benzylic Alcohols Catalyzed by a Boronic Acid/Oxalic Acid System

2017

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“…Compound 18 as a suitable surrogate for the spermidine part of the target was readily prepared from 1,3-diaminopropane 15, which was monoacylated with methyl 5-hexenoate followed by conversion of the remaining amine in 16 into the corresponding o-nitrobenzenesulfonyl (nosyl, Ns) derivative 17 (32,33) (Scheme 4). Taking advantage of the higher acidity of the sulfonamide (34), a selective N-alkylation of 17 with 1,4-dibromobutane was achieved to give product 18 on a multigram scale.…”

Section: Resultsmentioning

confidence: 99%

Catalysis-based enantioselective total synthesis of the macrocyclic spermidine alkaloid isooncinotine

Scheiper

Glorius

Leitner

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

129

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A concise and efficient total synthesis of the spermidine alkaloid (؊)-isooncinotine (1) incorporating a 22-membered lactam ring is outlined. The approach is largely catalysis-based, involving a selective iron-catalyzed alkyl-aryl cross-coupling reaction of a difunctionalized pyridine substrate, a heterogeneous asymmetric hydrogenation step to set the chiral center of the target, and a highly integrated ring-closing metathesis͞hydrogenation sequence to forge the saturated macrocyclic edifice in a single operation. Despite the prevalence of the biogenetic bases spermidine and spermine in nature and their widespread use as tools in biochemical research (1), little is known about the physiological properties of the small but structurally rather unique class of alkaloids incorporating these polyamines into their macrocyclic skeletons (2-4). This may be due, in part, to the difficulties in obtaining pure samples of these compounds from the natural sources † as well as to the fact that most syntheses described thus far provided only racemic material. Prototype spermidine alkaloids are (Ϫ)-isooncinotine (1), (Ϫ)-oncinotine (2), (Ϫ)-neooncinotine (3), and oncinodin-12-one (4), which were isolated from the stem bark of Oncinotis nitida and Oncinotis tenuiloba (Apocynaceae) (5-7) and have been repeatedly targeted in the past (8-12) (Fig. 1). Only recently has one member of this series (i.e., compound 2) been made available in an optically active form through total synthesis by using a diastereoselective 1,3-dipolar cycloaddition for the formation of the stereogenic center at the junction of the piperidine and the macrocyclic ring (13).In pursuit of previous work in the field of polyamine alkaloids (14, 15), we were prompted to develop a complementary, practical, and potentially scaleable entry into this family of natural products, choosing the 22-membered macrolactam (Ϫ)-isooncinotine 1 as our initial target. The envisaged route, however, should not only provide material for further evaluation but also meet a set of stringent chemical criteria. Specifically, it is felt that contemporary organic chemistry must (i) prioritize catalysis-based bond formations, (ii) try to control absolute stereochemistry by asymmetric catalysis, and (iii) aim at high convergence combined with an overall ''economy of steps'' (16). Furthermore, the total synthesis of 1 should provide us with the possibility to scrutinize methodology developed in our laboratories. Outlined below is the successful reduction of this plan to practice. Materials and MethodsGeneral. All reactions were carried out under Ar in flame-dried glassware. The solvents used were purified by distillation over the drying agents indicated and were transferred under Ar: tetrahydrofuran (THF) (Na), CH 2 Cl 2 (P 4 O 10 ), MeCN, Et 3 N, pyridine, NMP, hexamethylphosphoramide (HMPA), tetramethylethylenediamine (CaH 2 ), dimethylformamide (DMF) (dibutyltin dilaurate͞Desmodur), MeOH, EtOH (Mg), and toluene (Na͞K). For flash chromatography, Merck silica gel 60 (230-400 mesh) was used. F...

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“…We have shown that the nitrobenzenesulfonyl (Ns) moiety is available as both a protecting and activating group of amino group for flexible and practical synthesis of these compounds. 8,9) More recently, some of the present authors reported that thermospermine (2) plays a key role in regulation of cell division and differentiation in plant meristems. 10) Inspired by this interesting biological activity, we wished to synthesize thermospermine (2) and related compounds on a large scale for biological testing and mechanistic investigations.…”

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confidence: 77%

Practical Synthesis of Spermine, Thermospermine and Norspermine

Kariya

Asanuma

Inai

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

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Polyamines, such as spermine (1), thermospermine (2) and norspermine (3), are widely distributed in nature, and have multiple biological activities. In addition, many of their conjugates have potential for pharmacological use. Here, we present a solid-phase synthesis using our nitrobenzenesulfonyl (Ns) strategy, which can provide 1, 2 and 3 on a gram scale. This approach should be suitable for facile construction of a diverse library of polyamines.

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Ns strategies: a highly versatile synthetic method for amines

Cited by 498 publications

References 31 publications

Direct Sulfonamidation of Primary and Secondary Benzylic Alcohols Catalyzed by a Boronic Acid/Oxalic Acid System

Direct Sulfonamidation of Primary and Secondary Benzylic Alcohols Catalyzed by a Boronic Acid/Oxalic Acid System

Catalysis-based enantioselective total synthesis of the macrocyclic spermidine alkaloid isooncinotine

Practical Synthesis of Spermine, Thermospermine and Norspermine

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