Synthesis of 1s,2r,3s,4r,5r-methyl[2,3,4-trihydroxy-5-(hydroxymbthyl)cyclopentyl]amine: a potent α-mannosidase inhibitor

Farr, Robert A.; Peet, Norton P.; Fang, Nohinder S.

doi:10.1016/s0040-4039(00)97253-8

Cited by 69 publications

(42 citation statements)

References 18 publications

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“…Furthermore, the fact that the 4-epimer 54 of 52 completely lacked activity suggests that substituents located on theface at C-5 are important. Farr et al [23] reported synthesis of a strong mannosidase inhibitor, amino(hydroxymethyl) cyclopentanetriol 71 with a 1L-(1,2,4/3,5) configuration, and demonstrated good overlap between 71 and the mannopyranosyl cation on molecular modeling [16a], Fig. (12).…”

Section: Structure-inhibitory Activity Relationships Of Aminocyclopenmentioning

confidence: 99%

Design and Synthesis of Aminocyclopentanol Glycosidase Inhibitors: Modification of Mannostatin A and Trehazolamine

Ogawa¹,

Kanto²,

Uchida

2010

CBC

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Convenient synthesis of the -mannosidase inhibitor mannostatin A from myo-inositol is described by a method, which is generally applicable for provision of aminocyclopentanols of biological interest. Elucidation of structure-inhibitory activity relationships was carried out by chemical modification, leading to discovery of a very potent amino(methoxy)cyclopentanetriol. Similar studies of the trehalase inhibitor trehazolin stimulated development of a new type of aminocyclopentanol glycosidase inhibitor featuring ring contract mimicking of valiolamine, with implications for understanding of the structure and activity relationships of glycosidase inhibitors of this type.

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Section: Structure-inhibitory Activity Relationships Of Aminocyclopenmentioning

confidence: 99%

Design and Synthesis of Aminocyclopentanol Glycosidase Inhibitors: Modification of Mannostatin A and Trehazolamine

Ogawa¹,

Kanto²,

Uchida

2010

CBC

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“…It became apparent that the more the structures resembled mannostatin A (1), the greater their inhibitory potential. Farr [29] reported the synthesis of a strong mannosidase inhibitor, amino(hydroxymethyl)cyclopentanetriol 36, with a 1-(1,2,4/3,5N) configuration, and demonstrated good overlap between 36 and the mannopyranosyl cation by molecular modeling ( Figure 1 and Table 2). [16] Recently, Jäger [30] described the synthesis of two stereoisomers, 37 and 38, having 1-(1,2,4,5N/3) and 1 L-(1,2/3,4,5N) configurations, respectively.…”

Section: Biological Assaymentioning

confidence: 99%

Chemical Modification of the α‐Mannosidase Inhibitor Mannostain A: Synthesis of a Potent Inhibitor 1L‐(1,2,3,5/4)‐5‐Amino‐4‐O‐methyl‐1,2,3,4‐cyclopentanetetrol

Ogawa¹,

Morikawa²

2005

Eur J Org Chem

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Demethylthio‐, S‐demethyl‐, and S‐ethyl derivatives of the α‐mannosidase inhibitor, mannostasin A, were synthesized and evaluated for their inhibition of Jack bean α‐mannosidase with the prime objective of elucidating the role of the methylthio group. All methylthio derivatives had significantly lowered inhibitory potentials. However, one mannostatin A analogue with a methoxyl instead of the methylthio group exhibited about twofold enhancement of the activity. The structure and inhibitory activity relationships of mannostatin A and related compounds are discussed in light of our results. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

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“…± Several naturally occurring cyclopentane derivatives 1 ) are notable glycosidase inhibitors 2 ), such as trehazoline [3], allosamidine [4], and the mannostatins [5 ± 7]. Further cyclopentane-derived glycosidase inhibitors were prepared by Farr et al [8], J‰ger and co-workers [9] [10], Lundt and co-workers [11], Ganem and coworkers [12], Mehta and Mohal [13], and Reymond and co-workers [14 ± 16]. We synthesized and tested two bicyclo[3.1.0]hexanes (−cyclopropanated cyclopentanes×) in the context of a comparison of the mechanism of action of snail b-mannosidase with the one of the b-glucosidases from C. saccharolyticum and from sweet almonds [17].…”

mentioning

confidence: 99%

“…The first general method for the transformation of monosaccharides to cyclopentanes is based on a fragmentation and intramolecular 1,3-dipolar cycloaddition [18]. Intramolecular 1,3-dipolar cycloadditions of oximes [19], nitrile oxides [9] [20], and azomethine imines [21] have also been widely exploited for the synthesis of functionalized cyclopentanes [8]. Other methods for the transformation of carbohydrates into cyclopentanes 3 ) are based on free radical cyclizations 4 ) of alkenes [11] [25], aldehydes [26], hydrazones [27], and oxime ethers [16] [28], on carbanion cyclizations [14] [29] [30], tandem aldol-Wittig-type reactions [31], DielsÀAlder cycloadditions [32], [2 2] photocycloaddition [33], ring closing metathesis [34], rearrangements [23] [35] including a ring contraction [36], on the PausonÀKhand reaction [37], and the RambergÀB‰cklund rearrangement [38].…”

mentioning

confidence: 99%

Synthesis and Oxidation of N‐Aminoglyconolactams: A Synthesis of Mannostatin A

Vasella

2004

Helvetica Chimica Acta

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The N-amino-ribono-1,5-lactam 4 was prepared in two high-yielding steps from the known methanesulfonate 2. Oxidation of 4 with t-BuOCl in the presence of 2,6-lutidine afforded the tetrazene 6 (63%). Oxidation with MnO 2 gave the deaminated lactam 7 (40%), which was also obtained, together with the lactone 8, upon oxidation of 4 with PhSeO 2 H. Oxidation with Mn(OAc) 3 /Cu(OAc) 2 provided the lactam 7 as the major and the dimer 9 as the minor product. Oxidation of 4 with 3 equiv. of Pb(OAc) 4 in toluene at room temperature gave two cyclopentanes, viz. the acetoxy epoxide 10 and the diazo ketone 11 in a combined yield of 78%. Oxidation with Pb(OBz) 4 provided 11 and the crystalline benzoyloxy epoxide 12. The crystal structure of 12 was established by X-ray analysis. The N-amino-glyconolactams 41, 46, and 51 were prepared similarly to 4. Their oxidation with Pb(OAc) 4 provided the diazo ketones 56, 57, and 58 as the only isolable products. Oxidation of the N-aminomannono-1,5-lactam 55 with Pb(OAc) 4 in the presence of DMSO gave the sulfoximine 59. Mannostatin A, a strong a-mannosidase inhibitor, was synthesized from the acetoxy epoxide 10 (obtained in 48% from 4) in seven steps and in an overall yield of 45%. . This synthesis renewed our interest in the transformation of carbohydrates into cyclopentanes. Carbohydrates indeed appear to be ideal starting materials for the synthesis of highly functionalized, enantiomerically pure cyclopentanes. The first general method for the transformation of monosaccharides to cyclopentanes is based on a fragmentation and intramolecular 1,3-dipolar cycloaddition [18]

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Synthesis of 1s,2r,3s,4r,5r-methyl[2,3,4-trihydroxy-5-(hydroxymbthyl)cyclopentyl]amine: a potent α-mannosidase inhibitor

Cited by 69 publications

References 18 publications

Design and Synthesis of Aminocyclopentanol Glycosidase Inhibitors: Modification of Mannostatin A and Trehazolamine

Design and Synthesis of Aminocyclopentanol Glycosidase Inhibitors: Modification of Mannostatin A and Trehazolamine

Chemical Modification of the α‐Mannosidase Inhibitor Mannostain A: Synthesis of a Potent Inhibitor 1L‐(1,2,3,5/4)‐5‐Amino‐4‐O‐methyl‐1,2,3,4‐cyclopentanetetrol

Synthesis and Oxidation of N‐Aminoglyconolactams: A Synthesis of Mannostatin A

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