Nucleosides. LXV. Synthesis of New Pteridine–N8–Nucleosides
A general synthetic approach to various isoxanthopterin‐nucleosides starting from 6‐methyl‐2‐methylthio‐4(3H), 7(8H)‐pterdinedione (1) has been developed. Ribosylation with 1‐O‐acetyl‐2,3,5‐tri‐O‐benzoyl‐β‐d‐ribofuranose via the silyl‐method led to 2 and reaction with 1‐chloro‐2‐deoxy‐3,5‐di‐O‐p‐toluoyl‐α‐d‐ribofuranose using the DBU‐method afforded 28. Protection of the amide function at O4 by benzylation to 5 and by a Mitsunobu reaction with 2‐(4‐nitrophenyl)ethanol to 29 gave soluble intermediates which can be oxidized to the corresponding 2‐methylsulfonyl derivatives 8 and 30, respectively. Nucleophilic displacement reactions of the highly reactive 2‐methylsulfonyl functions by various amines proceeded under mild conditions to isoxanthopterin‐N8‐ribo‐ (11–17) and 2′‐deoxyribomucleosides (31–33). Debenzylation can be achieve by Pd‐catalyzed hydrogenation (9 to 19) and cleavage of the npe‐protecting group (31, 32 to 34, 35) works well with DBU by β‐elimination. #See Ref. 1. †In honor and celebration of the 70th birthday of Professor Leroy B. Townsend.
Fluorescence properties of a new guanosine analog incorporated into small oligonucleotides.
The fluorescence properties of 3-methyl-isoxanthopterin (3-MI) incorporated into different oligonucleotides have been determined. This highly fluorescent guanosine analog has its absorption and fluorescence spectra well resolved from those of the normal nucleotides and the aromatic amino acids. The small shifts observed in absorption and fluorescence emission spectra upon incorporation of 3-MI into these oligonucleotides are consistent with a general solvent effect and do not suggest any contribution from the position of the probe from the 5' end, the sequence of nucleotides immediately 5' or 3' to the probe, or the single- or double-stranded nature of the oligomer. However, steady-state and time-resolved fluorescence studies indicate that the presence of a purine immediately 5' or 3' to the probe results in some dynamic but mostly static quenching in the single-stranded oligomer. Furthermore, a 3' purine is more effective than a 5' purine, and an adenine appears to be more effective than a guanine for these static quenching interactions. Formation of the double-stranded oligomer leads to an additional loss of quantum yield, which can also be ascribed primarily to static quenching. These results show that this new class of spectrally enhanced fluorescent purine analogs will be able to provide useful information concerning the perturbation of nucleic acid structures.
A technique for large-field, superficial electron therapy.
The application of electron beams to radiation therapy has received increased attention in recent years. This interest stems largely from the special characteristics of the electron depth-dose distribution; the fall-off in depth dose near the end of the range of the electrons is particularly rapid for electron beams having energies less than about 10 Mev. Such an electron beam is suitable for the treatment of widespread, superficial lesions, where it is desirable to minimize the dose to deep tissues. All the common sources of super-voltage x-rays, apart from radioactive substances, are inherently capable of producing an external beam of electrons, though with varying degrees of complexity. Electrons of about the energy suitable for superficial therapy (several Mev) may be used to produce an x-ray beam which is sufficiently penetrating for the treatment of even the deepest lesions. The Stanford medical linear accelerator was designed to provide both x-rays and electron beams. The accelerator and its applic...