Synthesis of Oxazole Analogs of Streptolidine Lactam

Abstract

The streptolidine lactam is an amino acid constituent of streptothricin antibiotics, which inhibit protein synthesis by targeting the bacterial ribosome but suffer from toxicity as a result of the basicity of the aminoimidazole scaffold in the natural products. On the basis of the streptolidine structure, we designed and synthesized oxazole analogs with six‐ and seven‐membered lactam rings as building blocks for RNA‐targeted ligands. These analogs benefit from a dense network of hydrogen‐bond donors and acceptors within a rigid nonplanar heterocyclic system that has attenuated basicity.

Poly[3-methyl-1,3-oxazolidin-2-iminium[µ3-cyanido-tri-µ2-cyanido-κ9C:N-tricuprate(I)]]

“…The four atoms O1, C2, N3, N7 are strictly coplanar, but the constraints of the five-membered ring and its asymmetry force significant deviations from the idealized 120 • angles: the internal angle is reduced to 114.1(3) • , while the external angle N7-C2-N3 at 127.2(4) • is much larger than the angle N7-C2-O1, at 118.8(4) • . A similar geometry for this portion of the cation is seen in the three X-ray structures of similar iminium cations mentioned earlier [8][9][10], even in reference [8], where there is no substituent on N3. Other bond lengths and angles seem normal.…”

“…Oxazole synthesis has been achieved in at least fifteen different types of reactions [4], but we are not aware of a reaction similar to that reported here. There is less literature on the 2-iminium derivatives, and a search of the Cambridge Structural Database (CSD) [7] indicated only three crystallographic studies of their 2-iminium salts [8][9][10]. Reference 8 gives the structure of an oxaolidin-2-iminium ring with a seven-membered ring fused at C4 and C5, whereas the other references refer to the simple ring with various substituents.…”

Oxazoles for click chemistry II: synthesis of extended heterocyclic scaffolds

“…2 Moreover, in the area of peptidomimetics, oxazole-based scaffolds, backbones and amino acid analogues continue to provide a diverse array of compounds for pharmacological evaluation in numerous therapeutic areas. 3 We are presently conducting studies entailing the inhibition of dental biofilm formation using both the trisubstituted oxazole scaffold and the techniques of click chemistry. Porphyromonas gingivalis is a major pathogen associated with periodontal disease and this organism colonizes the dental biofilm by interacting with oral streptococci.…”

Asymmetric Total Syntheses of ent-Ascospiroketals A and B

“…Epoxidation of 11a or 11b with the classical NaOH/H 2 O 2 in methanol was found to be sluggish (about 20% conversion over 24 h), while extended reaction time (2–4 days) led to significant retro-aldol reaction of 11a , 11b , and 6 . Since most relative epoxidation conditions (K 2 CO 3 /H 2 O 2 /MeOH, t -BuOOH/NaH/THF, t -BuOOH/DBU/CH 2 Cl 2 , t -BuOOH/Amberlyst21/THF, and DMDO/CH 2 Cl 2 ) failed, we decided to temporarily protect the troublesome alcohol as its triisopropylsilyl (TIPS) ether. Gratifyingly, the TIPS ether was resistant to desilylation and suppressed the undesired retro-aldol reaction under the epoxidation conditions ( t -BuOK/ t -BuOOH/THF), which produced 6 in 78% overall yield after desilylation with TBAF.…”