Synthesis and reactions of deuterated 2-(alkylimino)-3-nitrosooxazolidines, 3-alkly-1-(2-hydroxyethyl)-1-nitrosoureas, and related compounds as possible intermediates in the aqueous decomposition of 3-alkyl-1-(2-chloroethyl)-1-nitrosoureas

Journal Article · Thu Jan 01 00:00:00 EST 1981 · J. Org. Chem.; (United States)

DOI:https://doi.org/10.1021/jo00325a011· OSTI ID:6197632

Lown, J W; Chauhan, S M.S.

Decomposition of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea-..cap alpha..-d/sub 2/(CCNU-..cap alpha..-d/sub 2/) (7) in pH 7.2 phosphate buffer or of CINO-..cap alpha..-d/sub 2/ (9) or CHNU-..cap alpha..-d/sub 2/ (8) with the addition of chloride ion gives rise to the same spectrum of products, including deuterium-free acetaldehyde (29), a mixture of the two deuterio-2-chloroethanols, 2-hydroxy-2,2-dideuterioethyl cyclohexyl carbamates, and vinyl chloride containing one deuterium (i.e., opposite the results obtained in the corresponding reaction of BCNU-..cap alpha..-d/sub 4/). The products were identified and the number and position of the deuterium labels determined by GC/MS. The results are interpreted in terms of two decomposition pathways for CCNU. The first decomposition pathway operating for CCNU is via an intermediate-2-chloroethanediazohydroxide or the equivalent 2-chloroethyl cation in agreement with the results of other workers. The second pathway may involve reversible conversion of CCNU-..cap alpha..-d/sub 2/ (7) to CINO-..cap alpha..-d/sub 2/ (9) and then ring opening of the latter to CHNU-..cap alpha..-d/sub 2/ (8). Independent decomposition of 8 provides evidence for its conversion to a 1.1-dideuterio-2-hydroxyethanediazohydroxide (41) leading to the isolated carbamates 36 and 44. The intermediacy of species 41 may account for the formation of 2-hydroxyethylated nucleosides observed when (2-chloroethyl)nitrosoureas react with DNA. An alternative ring-opening reaction of 9 leads to a 2-hydroxydiazoethyl cyclohexylcarbamate species (37), elimination of which and attack by halide ion may account for the vinyl halide species formed. Further evidence in support of these competing pathways employing additional specifically deuterated intermediates is described and discussed.

• Research Organization: Univ. of Alberta, Edmonton
• OSTI ID: 6197632
• Journal Information: J. Org. Chem.; (United States), Vol. 46:12
• Country of Publication: United States
• Language: English

Related Subjects

37 INORGANIC
ORGANIC
PHYSICAL AND ANALYTICAL CHEMISTRY
62 RADIOLOGY AND NUCLEAR MEDICINE
NITROSO COMPOUNDS
DEUTERATION
UREA
ANTINEOPLASTIC DRUGS
CHEMOTHERAPY
DEUTERIUM COMPOUNDS
NEOPLASMS
AMIDES
CARBONIC ACID DERIVATIVES
CHEMICAL REACTIONS
DISEASES
DRUGS
HYDROGEN COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
THERAPY
400303* - Organic Chemistry- Isotope Exchange & Isotope Separation- (-1987)
550600 - Medicine