Nitrile Oxides, Nitrones, and Nitronates in Organic Synthesis : Novel ...

100 NITRILE OXIDES
COX-2 selectivity was evaluated in vitro by using the human whole blood assays
of COX isoenzyme activity. Three compounds, not bearing the sulfonamide group
present in valdecoxib, have been found to be selective COX-1 inhibitors.
A total synthesis of ( + )-vinblastine widely used in cancer chemotherapy,
has been reported. It includes the synthesis of (–)-vindoline. 1,3-Dipolar cycloaddition
of a nitrile oxide has played an important role in the preparation of the
indoloazacycloundecane moiety, whose coupling with (–)-vindoline occurs with
the desired stereochemistry, leading to an intermediate readily transformed to the
target ( + )-vinblastine (492).
The synthesis of multivalent neoglycoconjugates by 1,3-dipolar cycloaddition
of nitrile oxides and alkynes has been reported (493). The nitrile oxides have
been generated in situ in the presence of alkynyl derivatives, allowing the access
to homo and hetero multivalent systems containig O- and C-linked glycosides
and isoxazole bridges.
The synthesis of the spiroisoxazoline natural product ( + )-calaÞanin 447 has
been reported, using asymmetric nucleophilic epoxidation and nitrile oxide cycloaddition
as key steps. Syntheses and spectral analyses of all calaÞanin stereoisomers
lead to unambiguous assignments of relative and absolute stereochemistry
(494).
Br
O
N
O
O
O
NH
HN
(CH 2)4
447
The 1,3-dipolar cycloaddition of nitrile oxides and 2-methylfuran provides
suitable precursors for α-amino acids such as L-furanomycin 448 that contains
a dihydrofuran ring (495). By using a chiral nitrile oxide derived from mannitol
bis(acetonide), the enantiomerically pure furoisoxazoline 449 has been obtained.
Hydroboration–oxidation of the latter leads to the hydroxy-substituted annulated
THF derivative 450, which is converted via dihydrofuran 451 to furanomycin
448 in enantiomerically pure form (Scheme 1.55).
A concise and efÞcient asymmetric synthesis of L-( + )-carbafuranomycin 452,
a novel analog of L-( + )-furanomycin, which is an unusual antibiotic amino
acid of great interest, due to its activity as an isoleucine antagonist, has been
reported (496). The synthesis starts with the 1,3-dipolar cycloaddition of a chiral
nitrile oxide (obtained in situ from hydroximinoyl chloride 453 via slow addition
of NEt3) with cyclopentadiene. Then methylation of cyclopentenyl acetate 454,
O
O
O
N
O
Br