Mannosidase mannostatin

Base-catalyzed nitromethane cyclization of the dialdehyde generated by periodate oxidation of 1,2-O-cyclohexylidene-myo-inositol affords the nitrodiol with 1,4/2,3,5-configuration. This is converted into the a-mannosidase inhibitor, mannostatin A (Eq. 3.60).98... 

Since the isolation of the chitinase inhibitor allosamidin from Streptomyces [90], the aminohydroxy-substituted cyclopentanes have been recognized as powerful and specific inhibitors of glycosidases [91]. The synthesis of (+) [92], as well as of racemic [93] mannostatin, which is a strong mannosidase inhibitor, should be mentioned here (Fig. 1). 

Mannostatin A, a pentasubsthuted amino-cyclopentane produced by Streptoverticillium verticillus var quintum ME3-AG3 [113], is also a specific inhibitor of a-D-mannosidase and has shown anti-metastatic activity [114],... 

Irradiation of pyridinium perchlorate in dilute perchloric acid (Xirr = 254 nm) is reported to give an amino diol which can be acetylated to the corresponding amido-diacetate (186 R = Ac), and which itself can be converted into the a-mannosidase inhibitor (+)-mannostatin A (187). The photochemical rearrangement of 1-acetyl-l,2-dihydroquinoline-2-carbonitriles to 3,1-benzoxazines and cycloprop[b]indoles has been described, and photo-... 

The a-mannosidase inhibitors mannostatin A (CsHijNOjS, Mr 179.24, mp. 121 C) and mannostatin B (C H 3N04S, Mr 195.24), isolated from Streptover-ticillium verticillus var. quintum, represent a new structural type. 

Mannosidase Inhibitors see glycosidase inhibitors. Mannostatin A and B see glycosidase inhibitors. 

Three deoxy-analogues of mannostatin A have been synthesized conventionally from known precursors. 1-Deoxy- and 3-deoxymannostatin A were produced from precursor 155, while a 2-deoxy-analogue was elaborated from 156. These compounds displayed weak or no inhibition of a-mannosidase. ... 

Mannostatins A an B, newly discovered inhibitors of amino-methylthio-cyclopentanetriol derivatives (30) and (31) respectively. 

In another example of the power of amine nucleophiles in the AAA reaction, Trost reported a highly enantioselective route to mannostatin A (77), a specific nanomolar inhibitor of a-D-mannosidase. Once again a desymmetrization strategy was employed, cyclizing meso substrate 75 in an intramolecular AAA reaction to give adduct 76. While other ligands provided inefficient in this task, the diphenylphosphino benzoic acid-based ligand 59 delivered key intermediate 76 in 97% ee, which was subsequently converted to mannostatin A (77). 

---