No abstract

Reaction of (^-CsHslMÍCOMNO) (M = Mo or W) (1) with LiC=CR (2) and subsequent addition of an electrophile leads either to a vinylidene or an ?y2-alkyne metal complex, [( 5-C5H5)(CO)(NO)]M=C=*,C(R)(R') derivatives are formed when alkyl or aryl acetylides (R = alkyl or CeHs) and either C-electrophile or dilute acid (R' = CH3 or H) are used.[(^5-C5H5)(CO)(NO)]M(R-C=C-R') (R = (CH3)3Si, CH3, allyl, or C6H5; R' = (CH3)3Si) is formed either when LiC=C-Si(CH3)3 is used and the addition product is trapped by allylbromide, trifluoromethanesulfonate, or (trimethylsilyl)chloride, or when the addition product of LiC=C-CeHs with 1 is trapped by (trimethylsilyl)chloride. The structure of [(^-CsHsXCO)-(NO)]W[H3C-C=C-Si(CH3)3] was determined by X-ray diffraction. Under the conditions used here, independent of the identity of the acetylide or electrophile, (7/5-CsHs)Cr(CO)2-(NO) leads only to the carbene complexes [(?75-C5H5)(CO)(NO)]Cr=C(OCH3)(C=C-R) (R = CeHs or (CH3)3Si). Addition of secondary amines to carbene complex [(^-CsHsXCOXNO)]-Cr=C(OCH3)(C=C-CeHs) is discussed. Synthesis of [(775-C5H5)(CO)(NO)]W=C=CH2 is described.

A protected, unsymmetrical bismethylene triphosphate analogue was prepared by sequential Michaelis-Arbuzov reactions on ethyl bis(halomethyl)phosphinates. This species was monodeprotected at one of the terminal phosphonate groups in high yield. The resulting monodeprotected compound was used to achieve the first syntheses of the bismethylene triphosphate analogues of UTP and CTP.

Cytidine triphosphate synthetase (CTPS) catalyzes the formation of cytidine triphosphate from glutamine, uridine-5'-triphosphate (UTP), and adenosine-5'-triphosphate. Inhibitors of CTPS are of interest because of their potential as therapeutic agents. One approach to potent enzyme inhibitors is to use analogues of high energy intermediates formed during the reaction. The CTPS reaction proceeds via the high energy intermediate UTP-4-phosphate (UTP-4-P). Four novel analogues of uridine-4-phosphate (U-4-P) and 3-deazauridine-4-phosphate (3-deazaU-4-P) were synthesized in which the labile phosphate ester oxygen was replaced with a methylene and difluoromethylene group. The methylene analogue of U-4-P, compound 1, was prepared by a reaction of the sodium salt of tert-butyl diethylphosphonoacetate with protected, 4-O-activated uridine followed by acetate deprotection and decarboxylation. It was found that this compound undergoes relatively facile dephosphonylation presumably via a metaphosphate intermediate. The difluoromethylene derivative, compound 2, was prepared by electrophilic fluorination of protected 1. This compound was stable and did not undergo dephosphonylation. Synthesis of the methylene analogue of 3-deazaU-4-P, compound 3, was achieved by ribosylation of protected 4-(phosphonomethyl)-2-hydroxypyridine. Electrophilic fluorination was also employed in the preparation of protected 4-(phosphonodifluoromethyl)-2-hydroxypyridine which was used as the key building block in the synthesis of difluoro derivative 4. These compounds represent the first examples of a nucleoside in which the base has been chemically modified with a methylene or difluormethylenephosphonate group.