Cleavage Yielding Hydroxamates

Conversion of solid-supported hydroxamates to aldehydes is a useful tool for the generation of C-terminal peptide-aldehydes. Martinez et aL firstly used LiAlH4-reduction for the cleavage of hydroxamates from solid supports and succeeded in synthesizing tripeptide aldehydes that could be obtained in about 40% yield after purification [83]. Reduction of Weinreb amides on... 

The ring cleavage behavior of cyclopentyl nitrite has been used in an interesting synthesis of cyclic hydroxamic acids. Thus steroidal 17/8-nitrites (81) on photolysis yield the corresponding hydroxamic acids (82).29 This conversion can be rationalized in the following way (83 to... 

Aldehydes and ketones have also been prepared by nucleophilic cleavage of resin-bound O-alkyl hydroxamic acids (Weinreb amides [744]) with lithium aluminum hydride [745] or Grignard reagents (Entries 1 and 2, Table 3.41). Similarly, support-bound thiol esters can be cleaved with Grignard reagents to yield ketones [272], or with reducing agents to yield aldehydes (Entry 3, Table 3.41). Polystyrene-bound sele-nol esters (RCO-Se-Pol) react with alkynyl cuprates to yield alkynyl ketones [746]. 

A type 2 intramolecular /V-acylnitroso Diels-Alder reaction of hydroxamic acid 177 followed by catalytic hydrogenation of the double bond was employed for the synthesis of substituted bridged bicyclic derivative 178, as a single diastereomer (Scheme 75 <2002OL2637>). Cleavage of the N-O bond was performed by reduction with Na(Hg) amalgam and provided m-3,7-disubstituted azocane 9, as a single isomer in 80% yield. 

Rosse et al. described the oxidation of the resin-bound /3-sulfenyl hydroxamic acids A -sulfonyloxaziridines <2001SL538>. For example, oxidation of 143 with 33 afforded the corresponding sulfoxide 144 in 71% yield after cleavage of the resin with TFA. Apfel et al. in the preparation of some potent peptide deformylase inhibitors and antibacterial agents employed a similar transformation<2000JME2324>. 

Rearrangements. Hurd and Bauer" added tosyl chloride in chloroform to a suspension of the sodium salt of benzohydroxamic acid (1) in the same solvent, noted a vigorous reaction, and characterized the product as benzo-(phenylcarbonyl-hydroxamic) acid (6). They postulate that the initial product is the tosylate (3), that this is a much stronger acid than (1) and so abstracts sodium from the salt (2) to give the salt (4), which undergoes concerted cleavage and Lessen rearrangement to phenylisocyanate (5) and sodium tosylate. The phenylisocyanate is then captured by (1) to yield the final product (6). 

Cyclization of Hydroxamates i-Cysteine-derived thiazolidine hydroxamate ester 71 is cyclized to the thiazolidine-fused fS-lactams 72 using methyl sulfonyl chloride [63]. The cleavage of the thiazolidine ring with methoxycarbonylsulfenyl chloride afforded the monocyclic fS-lactam 74 (Scheme 3.28). An Sml2-mediated scission of the N-O bond in 72 followed by cleavage of the thiazolidine ring afforded the NH monocyclic -lactam 73 in reasonable yield (Scheme 3.28). 

Shea s group applied this type 2 A-acylnitroso intramolecular Diels-Alder cyclization to the synthesis of tricyclic BCD core of stenine. The C2-tethered cyclic diene 103 was converted to the corresponding hydroxamic acid by treatment with NH20H-HC1, which, upon oxidation with BU4NIO4, was converted to 104 as a 6 1 mixture of diastereomers. Reductive N-0 bond cleavage of 104 yielded the alcohol 105 and its diastereomer (not shown). Further elaboration of 105 provided the tricyclic core structure 106 of stenine (Scheme 4.22) [41],... 

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