Quinazolines natural

In 2006, the group of Ellman and Bergman apphed their rhodium-catalyzed C-H activation method (see details in Section 16.2.5.1) to the synthesis of vasicoline, a quinazoline natural product (Scheme 16.31) [13aj. In this synthesis,... 

The stabilizing influence in the hydrated cation is the amidinium resonance. If a solution of the cation is neutralized, a short-lived hydrated neutral molecule (4) (half-life 9 sec at pH 10) is obtained with an ultraviolet spectrum similar to that of the hydrated cation but shifted to longer wavelengths (5 m/ ). Supporting evidence can be derived from the anhydrous nature of the cation of 4-nitroiso-quinoline (pK 1.35), in which the nitro group has a similar electronic influence to that of the ring nitrogen atom N-I in quinazoline and where amidinium resonance is not possible. 

Alkaloids containing a quinazoline nucleus form a small but important group of natural products and have been isolated from a number of different families in the plant kingdom. The quinazoline alkaloids are of the four types (48), (49), (50), and (51). The structures of arborine, peganine, febrifugine, rutaecarpine, and evodi-amine have been elucidated by degradation and synthesis and are described in recent reviews on quinazoline alkaloids. ... 

Methoxyquinazoline and methyl iodide give the salt 72 (Y = 0), and, although the route for this reaction has not been investigated, there is a suggestion that the reaction occurs at N-3. A final decision concerning the nature of electronic and steric influences on quater-nization in the quinazoline ring must clearly await further work. 

Kinetic studies have been carried out on the displacement reactions of various chloroazanaphthalenes with ethoxide ions and piperi-dine. - 2-Chloroquinoxaline is even more reactive than 2-chloro-quinazoline, thus demonstrating the powerfully electrophilic nature of the -carbon atoms in the quinoxaline nucleus. The ease of displacement of a-chlorine in the quinoxaline series is of preparative value thus, 2-alkoxy-, 2-amino-, - 2-raethylamino-, 2-dimethyl-amino-,2-benzylamino-, 2-mercapto-quinoxalines are all readily prepared from 2-chloroquinoxaline. The anions derived from substituted acetonitriles have also been used to displace chloride ion from 2-chloroquinoxaline, ... 

Isolated and benzo-fused diazine rings are key structural elements in many natural and synthetic compounds of current interest. This contribution relates highlights from many of the studies on the diazines pyridazine, pyrimidine, pyrazine, and their benzo-fused derivatives cinnoline, phthalazine, quinazoline, quinoxaline, and phenazine published in English in the journal literature during 1996, as covered by Chem. Abstr. through volume 126, issue 5. 

The same approach was readily adaptable to solid-phase synthesis. A small library of unnatural derivatives of 140 was prepared with variation of the configuration and nature of R1 and R4 and with substitution on the benzene ring <2000JC0186>. Three natural alkaloids, Verrucine A, B, and Anacine, were synthesized by a similar pathway and the pyrazino[2,l- ]quinazoline as opposed to the benzodiazepine structure of Anacine was proved <2001JNP1497>. Fiscalin B and other derivatives were prepared by solid-phase synthesis using polyethylene glycol (PEG) resin <2002USP6376667>. 

Michael, J. P. 2000. Quinoline, quinazoline and acridone alkaloids. Nature Product Reports, 17 603-620. 

As we have already seen in several examples, the electron withdrawing nature of the nitrogen atoms in heterocyclic systems leads to a marked increase in their ability to participate in cross-coupling reactions. The triazolo[l,5-a]quinazoline system in 8.23. is a nice example, since not only the 5-chloro, but also its 5-tosyloxy derivative was shown to couple readily with 2-tributylstannyl-thiophene in 78% and 91% yield respectively.32 Interestingly, in case of the chloro derivative the addition of copper... 

Fig. 7 Natural products with a pyrazino[2,l- ]quinazoline-3,6-dione skeleton...

The methodology was successfully extended to a one-pot total synthesis of complex heterocyclic systems such as pyrazino [2,1-b] quinazolines 79, encountered in nature as alkaloids 80-82 (Scheme 50) [125]. To assemble the pyrazino[2,l-fo]quinazoline core, N-Boc protected amino acid 76 was employed instead of carboxylic acid 72 (Scheme 49) in the synthesis of the corresponding intermediate benzoxazinones 77. The subsequent reaction with an amine moiety of another amino acid ester 78 was accompanied by concomitant cleavage of the N-Boc protecting group and diketopiperazine-like cyclization (for the one-pot deprotection-cyclization reaction of N-Boc dipeptide esters to afford 2,5-piperazinedione under microwave dielectric heating, see [128]) to afford the target heterocycle 79. Hence, the total... 

---