Pyrrolo pyrimidine, synthesis from

Perhaps the most unique synthesis of a pyrrolo[2,3-, pyrimidine arises from a completely acyclic precursor. Thus, 180, upon reaction with guanidine in basic media, produces both rings, although undoubtedly one ring is formed first in situ (Equation 68). Good yields of 181 were obtained <1995CPB256>. 

At the conclusion, the total synthesis of rigidin (6) proceeded in nine steps and nearly 26% overall yield starting from 6-chlorouracil and ethyl 2,4-dimethoxybenzylglycinate. The utility of the acylative pyrrole annu-lation approach to a highly substituted pyrrolo[2,3-d]pyrimidine system was thus revealed. Next we chose to focus our attention on representative... 

Benhida described the synthesis of a 2-deoxy-C-nucleoside analogue and its phosphoramidite derivative featuring 6-(thiazolyl-5)-a-benzimidazole nucleobase (134). A more efficient route to the expanded adenosine analogue (135) was developed by Kool, who also described the synthesis of the expanded thymidine analogue (136) starting from 5-methylanthranilic acid. Both nucleosides were found to be efficient fluorophores. 3 -Cyanoethyl phosphoramidites of 6-methyl-3-(2 -deoxy-(3-D-ribofuranosyl)-3//-pyrrolo[2,3-d]pyrimidin-2-one... 

Yamanaka and associates developed a method for the synthesis of 2-butylindole from the Sonogashira adduct of ethyl 2-bromophenylcarbamate and 1-hexyne [97, 98]. Extension of that method to pyridines led to the synthesis of pyrrolopyridines [99]. However, the method was not applicable to the synthesis of pyrrolo[2,3-6/]pyrimidines. They then developed an alternative route involving an initial S Ar displacement at the 4-position of 4,5-dihalopyrimidine followed by a Sonogashira coupling at the 5-position [100]. Thus, 5-iodopyrimidine 200 was obtained from an S Ar displacement at the 4-position of a 4-chloro-5-iodo-2-methylthiopyrimidine (199). The subsequent Sonogashira reaction of 200 with trimethylacetylene at 80°C resulted in adduct 201, which spontaneously cyclized to pyrrolo[2,3-6/]pyrimidine 202. 

The formation of a nitrene adjacent to a double bond can be used in the synthesis of novel heterocyclic systems. For example, the azide 721 converts smoothly into the tricyclic product 722 on irradiation and the same modus operandi is used for the synthesis of pyrrolo[2,3-J]pyrimidines from substituted 4-azidopyrimidines . Aziridine formation is also encountered in the cyclization of 723 to the tetrahydroquinoline derivatives 724 . Other cyclizations provide routes to imidazoindoles 725 " or thienopyrroles 726 . ... 

Numerous syntheses have also been reported for arabinofuranosyl nucleoside analogues, prepared either conventionally from arabinofuranosyl derivatives or via 2,2-anhydro-nucleosides obtained from appropriate ribonucleosides. 5-Aza-cytosine-D-arabinoside has been synthesized and found to show similar antiviral activity to Ara-C(arabinosyl-cytosine). 7-a-, 7-<3-, 9-0 -, and 9- 3-arabino-furanosyl derivatives of 3-deazaguanine have also been prepared, but none showed any anti-tumour activity. 9-(o -D-Arabinofuranosyl)-8-aza[2- C]-adenine, 7-(/3-D-arabinofuranosyl)-pyrrolo[2,3-d]pyrimidine-4(3//)-one (15)," l-(a-D-arabinofuranosyl)- and l-(/3-D-xylofuranosyl)-4-nitropyrazole, and Ot-arabino-nucleosides of 5-fluoro-cytosine and -uracil derivatives have also been prepared. An improved synthesis of 9-(/3-D-arabinofuranosyl)-2-fluoro-adenine has been reported. The ratio of o to 3 anomers obtained by phase-transfer reaction of 2,3,5-tri-O-benzyl-D-arabinofuranosyl bromide with 6-chloro-2-thiomethyl-7-deazapurine varied with the quaternary ammonium salt used as a catalyst, although the jU-anomer predominated in every case. 2,2-Anhydro-nucleosides have been used to prepare l-j3-D-arabinofiiranosyl derivatives of 5-alkylthio-uracils, 5-ethyl-cytosine, and 5-ethyl-uracil, 8-alkylamino-purines, and 2-aralkylamino-l,4-dihydro-4-imino-pyrimidine hydrochlorides (16). ... 

Recently, Varquero and coworkers employed TosMIC in their synthesis of the core structure of 54 (Scheme 7.11) for access into the Variolins [30] (55-57), a family of alkaloids isolated from the spongeKirtpatrickia variolosa Kirkpatrick [31]. Variolins contain the rare pyrrolo[l,2-c]pyrimidine system and also claim to have antiviral and antiproliferative activities against P388 leukemia cells [31b]. 

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