reflux, 2 h

dbu, toluene reflux, 4h

Scheme 19 Synthesis of benzomalvins A and B [233,234]

1.1% (NOE)

major conformer (76%) [a]211D = -109.8°(c 1.0 MeOH)

minor conformer (24%) [a]22 2D = +77.10 (c 1.0 MeOH)

nation of 18, followed by dehydrobromination gave benzomalvin B as an E/Z mixture.

(-)-Benzomalvin A was found to be very unstable in solution affording a 76 : 24 equilibrium mixture of major and minor conformers at 23 ° C for 280 h in CDCl3 as determined by 1H NMR spectra (Fig. 4). The NOE measurements, and X-ray crystallographic analysis of the separable minor conformer, supported the assigned spatial proximity between N-Me and H-7 as shown. The minor conformer was shown to be (+)-invertmer based on the optical rotation [233,234].

Asperlicins, Circumdatin F, and Sclerotigenin

The quinazolinone annelation procedure described above by acylation of an amide group with 2-azidobenzoylchloride (37) followed by the Staudinger/ intramolecular aza-Wittig tandem reaction together with intramolecular aza-Wittig methods (see Sect. 2.2.2) has become known as the Eguchi aza-Wittig protocol [26,111,240] after its successful applications by Snider et al. to the synthesis of quinazolinobenzodiazepine alkaloids (Scheme 20) and the pyrazino[2,1-fr]quinazoline scaffold in the fumiquinazoline alkaloids (see Sect. 3.4.1) and to the preparation of ardeemin by Danishefsky et al. (see Sect. 3.4.3). As shown in Scheme 20, this method has been utilized for the synthesis of asperlicin C (93a), circumdatin F (93b) and sclerotigenin (19) by selective acylation ofthe more acidic anilide nitrogen ofbenzodiazepinediones 91 without the need for protecting groups, followed by TBP-induced cyclization of the 1-(2-azidobenzoyl)-1,4-benzodiazepine-2,5-dione derivative 92 [241].

Utilizing the Eguchi aza-Wittig protocol Snider et al. achieved the total synthesis of the more complex antibiotic (-)-asperlicin 20, known also for its potent cholecystokinin antagonist activity [76-79] (Scheme 21) [242]. L-Tryptophan-derived benzodiazepinedione 94 is converted into the fused quinazolinone 95.

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