RESUMO
A novel, versatile and modular route to unsymmetrical diborane(4) derivatives bearing either two different diol moieties or one diol and one diamine moiety is presented. Utilising the very basic approach of reacting a boron nucleophile with a boron electrophile to establish the B-B bond allows a simple variation of the two individual boron moieties. The copper(i) boryl complexes used as nucleophilic boron sources are readily accessible from commercially available symmetrical diborane(4) derivatives, whilst equally readily available boron halide derivatives are used as electrophiles. Seven previously inaccessible diborane(4) derivatives were obtained and fully characterised, including single crystal X-ray structure determinations, illustrating the broad scope of the method.
RESUMO
The unsymmetrical diborane(4) pinB-B((RN)2(C6H4)) (R = Me, Bn) reacts with [(Me3P)4Rh-X] (X = Me, OtBu) giving predominantly either [(Me3P)4Rh-Bpin] or [(Me3P)3Rh-B((RN)2(C6H4))] depending on X. At low temperatures in the presence of excess PMe3 the unprecedented equatorial boryl complex [(Me3P)4Rh-B((MeN)2(C6H4))] is formed.
RESUMO
PURPOSE: This trial was conducted to determine whether high-dose fluorouracil (FU) given as a weekly 24-hour infusion is more active than bolus FU + leucovorin (LV), and whether high-dose infusional FU can be modulated by LV. PATIENTS AND METHODS: A total of 497 patients with previously untreated metastatic colorectal cancer were randomly assigned to receive bolus FU 425 mg/m2 intravenously + LV 20 mg/m2 on days 1 to 5 and repeated on day 28 (FU + LV), or FU 2600 mg/m2 as a 24-hour infusion alone (FU24h) or in combination with 500 mg/m2 LV (FU24h + LV)-all given weekly x6 followed by a 2-week rest period. Survival was the major study end point. RESULTS: With a median follow-up of more than 3 years, survival did not differ among the treatment groups (median FU + LV, 11.1 months [95% CI, 10.2 to 15.0 months]; FU24h, 13.0 months [95% CI, 10.4 to 15.4 months]; FU24h + LV, 13.7 months [95% CI, 12.0 to 16.4 months]; P =.724). Progression-free survival (PFS) was significantly longer for FU24h + LV (median FU + LV, 4.0 months [95% CI, 3.4 to 4.9]; FU24h, 4.1 months [95% CI, 3.4 to 5.0]; FU24h + LV 5.6 months [95% CI, 4.4 to 6.7]; P =.029). The response rates in the subgroup of patients with measurable disease were 12%, 10%, and 17% for FU + LV, FU24h, and FU24h + LV, respectively (not significant). Occurrence of grade 3 and 4 diarrhea was higher in the FU24h + LV arm (22%) compared with the FU24h (6%) or FU + LV (9%) arms; however, stomatitis (11% in FU + LV v 3% in FU24h v 5% in FU24h + LV arms) and hematologic toxicity were higher in the bolus FU + LV arm. Global quality of life did not differ within the three arms. CONCLUSION: Neither FU24h + LV nor FU24h prolong survival, relative to bolus FU + LV. Leucovorin increases PFS if added to FU24h, but increases toxicity.