Azasugar synthesis

Kajimoto, T, Liu, K K-C, Pederson, R L, Zhong, Z, Ichikawa, Y, Porco, J A, Wong, C-H, Enzyme-catalyzed aldol condensation for asymmetric synthesis of azasugars synthesis, evaluation, and modeling of glycosidase inhibitors, J. Am. Chem. Soc., 113, 6187-6196, 1991. 

N-Acetylgjucosamine azasugars, synthesis using FDP aldolase, 24,26/ N-Acetylglucosaminyltransferases (GlcNAcT)Iandn... 

Synthesis of azasugars and alkaloids via ring-closing metathesis 99EJ0959. 

The aqueous aza-Diels-Alder reaction of an aldehyde and an amine hydrochloride with a diene is catalyzed by lanthanide(III) trifluoromethane sulfonates (Ln(OTf)3, triflates [24]). Some examples are reported in Schemes 6.12 and 6.13. With respect to uncatalyzed reactions, the lanthanide catalyst allows milder reaction conditions, increases the reaction yield and does not affect the diaster-eoselectivity of the reaction, but influences the regiochemistry as in the cycloaddition of 25 with 1,3-dimethyl-1,3-butadiene (Schemes 6.10 and 6.12). These results have been applied [24b-d] to the synthesis of azasugars (Scheme 6.14). 

Figure 10.30 Stereoselective synthesis of five- and seven-membered ring azasugars, N-alkylated fagomine derivatives, and of novel azasugar phosphonates.

Several examples of transition metal catalysis for the synthesis of piperidines appeared this year. Palladium catalyzed intramolecular urethane cyclization onto an unactivated allylic alcohol was described as the key step in the stereoselective synthesis of the azasugar 1-deoxymannojirimycin . A new synthetic entry into the 2-azabicyclo[3.3.1]nonane framework was accomplished through a palladium mediated intramolecular coupling of amine tethered vinyl halides and ketone enolates in moderate yields . A palladium catalyzed decarboxylative carbonylation of 5-vinyl... 

O. Lopez and M. Bols, Isofagomine, neouromycin and other 1-azasugars, imino sugars-related glycosidase inhibitors, in Imino sugars, from synthesis to therapeutic applications, ed. P. Compain and O. Martin, Wiley, 2007, pp. 131-151. 

In general, 2-amino-substituted oxazolines are more resistant to acid hydrolysis. For example, the 2-aminooxazoline moiety in the protected azasugar 316 was preserved during acid cleavage of a ketal in the hnal step of a trehazolin synthesis (Scheme 8.93). ° ... 

The availability and the rather similar substrate tolerances exhibited by most members within the families of related lyases fulfills the demand for a complete set of catalysts for a directed stereodivergent synthesis of a set of diastereomeric products from common synthetic building blocks [189]. The verification of this concept ( combinatorial synthesis ) has indeed been pursued in a different respect, and will be highlighted by pertinent examples for the synthesis of simple sugars and for the synthesis of azasugars , an emerging class of glycosidase inhibitors. 

Scheme 25. Stereodivergent synthesis of 1-dcoxy azasugars of the nojirimycin type by enzymatic aldolization followed by catalytic reductive amination. a) 1. Aldolase, DHAP 2. phosphatase 3. H2/Pd-C...

Heteroaromatic alkenes have been found to be especially useful substrates for the AA, since they offer a considerable potential for further synthetic transformations. Thus, in a most elegant application the product 12 obtained from vinylfurane (10) via the AA was used for the synthesis of azasugars like 13 as precursors toward deoxymannojirimycin [13]. 

A review on the use of the RCM reaction toward the synthesis of azasugars and alkaoids has been published <1999EJ0959>. 

A variety of amino-alcohol derivatives have been used as substrates for RCM approaches to piperidines. Representative examples of these methods are shown in Scheme 18 (32, <01TL1209> 33, <01TA817> 34, <02OL4499). Application of this chemistry to the synthesis of deoxy-azasugars and hydroxypyrrolizidines has been reported <01TL4079>. 

Numerous examples of cyclizations by attack of a nitrogen nucleophile on an electrophilic carbon leading to piperidines have been reported in recent literature these examples are illustrated by the synthesis of polyhydroxylated indolizidine scaffold 60 <2004JOC3139> and the synthesis of azasugar type compounds 61 (Scheme 39) <2004JME1930>. 

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