Allosamizoline

The phenylthionocarbonate procedure was also used for the cyclization of a 5-oxime-ether radical (Scheme 6) [17]. The stereochemical outcome of this reaction is almost identical with that observed for a closely related 6-methoxyhex-5-enyl radical cyclization [12,14]. A related glucosamine-derived radical cyclization has been employed for the synthesis of allosamizoline 13 [18]. Other examples in this area include the cyclization of... 

Abietic acid, 685 Adenosine acelonide. ent. 607 Allosamizoline, 602 Allylsiane... 

In 1986 the novel chitinase inhibitor (—)-allosamidin was discovered in fermentation broths of Streptomyces sp. 1713 by Sakuda and coworkers.1 (—)-Allosamidin is unusual inasmuch as it contains two N-acetyl-D-allosamine residues glycosidically linked P-1,4 to one another. In turn, this disaccharide is connected to a cyclopentanoid known as (—)-allosamizoline in the manner shown in Figure 11.1. 

A careful comparison of the (—)-allosamizoline structure with that of D-glucosamine reveals a perfect heteroatom chirality match at carbons 2, 3, and 4 (Scheme 11.1). Conceptually, one can arrive at (—)-allosami-zoline if one establishes a C—C bond between C(l) and C(5) in d-glucosamine, and one then appends an amino-oxazoline ring onto the... 

Let us return now to the (—)-allosamizoline question. If Kuzuhara s intention was to derive three of the target s chiral centres from... 

Clearly, in the Kuzuhara synthesis of (—)-allosamizoline, we have seen yet another powerful strategy for ring synthesis, namely ring-contraction, being used to excellent effect. 

The next phase of the synthesis was installation of the dimethylamino-oxazoline ring system. This was constructed from the oxazolidinone precursor 19. Oxazolidinone formation occurred when 25 was reacted with thionyl chloride. The more nucleophilic carbonyl of 19 was then O-alkylated with the Meerwein reagent to give an iminium ion that readily participated in a nucleophilic addition/elimination reaction with dime-thylamine to give 26. The final step of the synthesis was O-deacetylation of 26 with sodium methoxide to provide (—)-allosamizoline hydrochloride in 98% yield after acidification. 

Mechanistic analysis of some key steps in the Simpkins (—)-allosamizoline synthesis... 

Scheme 9. 5-Deoxysugars The 5-amino-5-deoxysugars (piperidinoses) nojirimycin (17), 1-de-oxynojirimycin (18), mannojirimycin (19) and galactostatin (20). The tetrahydropyrrol moiety of bulgecin A (21) and the allosamizoline unit 22 of allosamidine (23can also be considered as 5-deoxysugars. The derivation of 22 from the pool has already been proven...

Desymmetrization by means of this methodology was successfully applied to a synthesis of key intermediates for mosin B, aspicilin, ga/a-quercitol, and allosamizoline. ... 

Radical additions to 0-alkyl aldoximes, easily accessible from reducing sugars, have been exploited for the synthesis of allosamizoline, the aglycon of aUosamidin [334]. The C ring of anguidine has also been prepared by reductive carbocyclization of an aldehyde on an unsaturated ester [335]. 

---