Hydrogenolysis and stereochemistry of photodimers of thymine and thymidine

Abstract

Photolysis of 16. An aqueous solution (500 ml) of the ylide 16 (1.0 g) was irradiated with a high-pressure mercury lamp for 3 hr. After removal of the aqueous solvent, the products were purified by chromatography (silica gel, MeOH-CHCls, 3:5). The major product was 2-methyl-4-hydroxypyrimidine (100 mg, 22%) which was converted to the hydrochloride and identified by direct comparison with an authentic sample. A small amount of 1-arabinosyl-2-methyl-4(U7)-pyrimidinone (19) was also obtained.Dimethyloxosulfonium l-(5-0-Trityl-2-deoxy-/3-D-xylofuranosyl)-5-methyI-l,4-dihydro-4-oxo-2-pyrimidinemethylide (22). To the ylide prepared from NaH (0.85 g) and trimethyloxosulfonium chloride (5.5 g) in THF (150 ml) was added 2,3'-anhydro-l-(5-0trityl-2-deoxyxylofuranosyl)thymine26 (4.5 g) and the mixture was gently refluxed overnight. The precipitate was collected by filtration and washed several times with cold water to leave a colorless solid (2.0 g, 37%), which was recrystallized from MeOH-ether or aqueous EtOH to give colorless crystals: mp 203-205°; [a]25o -9.8°(c 20.5, MeOH); ir 3250 (OH), 1640 (C2), 1550, 1170 cm"1; uv X"',0H 280, 233 nm (log c 4.33, 4.31); X"'"0H 256 nm(log < 4.06).

Reversible Hydrolysis Reaction with the Spore Photoproduct under Alkaline Conditions

“…It is likely that the alcohol formation stabilizes the product, preventing the reverse reaction from occurring. After oxidizing the alcohol by potassium permanganate, the resulting carboxyl moiety can then react with the ureido group under acidic conditions, regenerating the cis-syn CPD …”

“…Via UV irradiation of the thymine base, both cis-syn and trans-syn CPDs were generated. The alkaline treatment of the trans-syn CPD readily broke the two N3–C4 bonds, resulting in the full-hydrolysis product (Scheme D) . In contrast, probably due to the maintained stacking interactions between the two thymine ring, the cis-syn CPD was considered as being unable to support the hydrolysis product formation upon hot alkaline treatment by the initial study .…”

“…The alkaline treatment of the trans-syn CPD readily broke the two N3–C4 bonds, resulting in the full-hydrolysis product (Scheme D) . In contrast, probably due to the maintained stacking interactions between the two thymine ring, the cis-syn CPD was considered as being unable to support the hydrolysis product formation upon hot alkaline treatment by the initial study . A later study, however, found that a 24-h treatment using 0.1 M NaOH at 75 °C did result in the full-hydrolysis product as shown in Scheme C .…”

“…After oxidizing the alcohol by potassium permanganate, the resulting carboxyl moiety can then react with the ureido group under acidic conditions, regenerating the cis-syn CPD. 45 Thus, the chemical structure of a given pyrimidine lesion largely determines its chemical property upon base treatment, i.e., its alkaline liability. Between dHdU and SP, although they share similar structures, the cross-link bond between the two thymine bases in SP likely places some restriction on the 3D structure, which provides the framework driving the occurrence of the reverse reaction, even though the negatively charged carboxyl moiety is a weak electrophile and the amide is a weak nucleophile.…”

“…45 In contrast, probably due to the maintained stacking interactions between the two thymine ring, the cis-syn CPD was considered as being unable to support the hydrolysis product formation upon hot alkaline treatment by the initial study. 45 A later study, however, found that a 24-h treatment using 0.1 M NaOH at 75 °C did result in the full-hydrolysis product as shown in Scheme 3C. 46 However, there was no attempt to reveal whether such a hydrolysis reaction is reversible as observed in the SP reaction here.…”