The role of IVS14+1 G > A genotype detection in the dihydropyrimidine dehydrogenase gene and pharmacokinetic monitoring of 5-fluorouracil in the individualized adjustment of 5-fluorouracil for patients with local advanced and metastatic colorectal cancer: a preliminary report.

AIM: We retrospectively investigated the relationship between IVS14+1 G > A genotype of the dihydropyrimidine dehydrogenase (DPD) gene with plasma concentration of 5-fluorouracil (5-FU) as well as adverse reactions in 80 patients with locally advanced or metastatic colorectal cancer. PATIENTS AND METHODS: Eighty patients with un-resectable locally advanced or metastatic colorectal cancer were treated with Folfox-6 regimen, which repeated every two weeks for at least three cycles. Single nucleotide polymorphisms for DPD gene were analyzed before chemotherapy by high-resolution melting (HRM) analysis. The plasma concentration of fluorouracil was measured by high performance liquid chromatography (HPLC) after continuous infusion of fluorouracil over 12 h in each cycle. The average values of plasma concentrations in each cycle were calculated, and the factors related to plasma concentration of 5-FU were screened by stepwise regression. RESULTS: All patients were divided into three groups according to the predictive confidence interval of plasma concentration of 5-FU, and the average plasma concentrations of fluorouracil in each cycle of these three groups were less than or equal to 26.83 mg/L, 26.83-40.62 mg/L, and more than 40.62 mg/L, respectively. Stepwise regression analysis showed that the plasma concentration of fluorouracil was associated with myelosuppression, hand-foot syndrome, diarrhea, overall survival (OS) and DPD genotype. In efficacy, the median progression-free survival PFS (mPFS) and OS (mOS) of group 2 and group 3 were both significantly higher than those of group 1. CONCLUSIONS: Among the advanced colorectal cancer patients receiving fluorouracil-based chemotherapy, those with plasma concentration of 5-FU above 26.83 mg/L can obtain better survival; for patients with heterozygous DPD IVS14+1 mutation, 5-FU dose should be appropriately reduced according to last plasma concentration to reduce adverse reactions, while the homozygous ones should avoid application of 5-FU and its derivatives.

Distant functionalization via incorporation of thiophene moieties in electrophilic reactions promoted by samarium diiodide

Methyl thiophene-2-carboxylate, methyl 3-(thien-2-yl)acrylate, and methyl 5,2'-bithiophene-2-carboxylate were utilized as the synthetic equivalents of pentanoate 5-anion, pentanoate 4,5-dianion, heptanoate 7-anion, and nonanoate-8,9-dianion. By the promotion of samarium diiodide, these thiophene-incorporating compounds reacted with aldehydes, ketones, and conjugated esters regioselectively at the thienyl rings. Long-chain esters with remote hydroxyl and carboxyl groups, including an antiarthritis agent, a shellac component, and an inhibitory agent of spore germination, were prepared after reductive desulfurization on Raney nickel.

Synthesis of

A series of 1,1'-dicinnamoylferrocenes were converted to the corresponding [3]ferrocenophane diols (4a-e) in a stereoselective manner by using samarium diiodide to effect the intramolecular coupling reaction, aldol reaction, and reduction in one-pot operation. The major reaction pathway might be derived from a samarium chelated transition state (I(A)()) having the moieties of s-cis enone and (Z)-enolate. A solid-state structure of such [3]ferrocenophane diol product showed that the cyclopentadienyl groups were in an eclipsed orientation and slightly tilted.

A stereoselective route to polysubstituted tetrahydroquinolines by benzotriazole-promoted condensation of aliphatic aldehydes and aromatic amines

By the promotion of benzotriazole (20 mol %), two molecules of anilines (or other arylamines) and two molecules of phenylacetaldehyde (or o-bromophenylacetaldehyde) condensed to give a series of 1,2,3,4-tetrahydroquinolines in a stereoselective manner. By the catalysis of SmI(2) or SmI(3), the N-(alpha-aminoalkyl)benzotriazoles derived from anilines and (R)-glyceraldehyde acetonide dissociated to the corresponding iminium and enamine species, which underwent asymmetric [4 + 2] cycloadditions to give optically active tetrahydroquinolines.