Total synthesis and biological activity of dolastatin 16

The total synthesis of dolastatin 16, a macrocyclic depsipeptide first isolated from the sea hare Dolabella auricularia as a potential antineoplastic metabolite by Pettit et al., was achieved in a convergent manner. Dolastatin 16 was reported by Tan to exhibit strong antifouling activity, and thus shows promise for inhibiting the attachment of marine benthic organisms such as Amphibalanus amphitrite to ships and submerged artificial structures. Therefore, dolastatin 16 is a potential compound for a new, environmentally friendly antifouling material to replace banned tributyltin-based antifouling paints. The synthesis of dolastatin 16 involved the use of prolinol to prevent formation of a diketopiperazine composed of L-proline and N-methyl-D-valine during peptide coupling. This strategy for the elongation of peptide chains allowed the efficient and scalable synthesis of one segment, which was subsequently coupled with a second segment and cyclized to form the macrocyclic framework of dolastatin 16. The synthetic dolastatin 16 exhibited potent antifouling activity similar to that of natural dolastatin 16 toward cypris larvae of Amphibalanus amphitrite

Basal cell adenocarcinoma on bulbar conjunctiva of third eyelid in a dog

An 8-year-old castrated Toy poodle presented with swelling and proptosis of the right third eyelid caused by an exophytic mass on the bulbar surface. Histologically, the mass was composed of stratified neoplastic basaloid cells, arranged in nests and interconnecting islands, which were mixed with tubular structures. Immunohistochemically, the basaloid cells were positive for p63 and cytokeratin (CK) 14, and the inner epithelial cells of the tubular structures were positive for CK7, CK8, and CK19. According to these findings, the mass was diagnosed as a basal cell adenocarcinoma. Although basal cell adenocarcinoma is rare in animals, it should be included in the list of differential diagnoses for superficial tumors of bulbar conjunctiva of third eyelid in dogs

Effective Synthesis and Antifouling Activity of Dolastatin 16 Derivatives

Some derivatives of dolastatin 16, a depsipeptide natural product first obtained from the sea hare Dolabella auricularia, were synthesized through second-generation synthesis of two unusual amino acids, dolaphenvaline and dolamethylleuine. The second-generation synthesis enabled derivatizations such as functionalization of the aromatic ring in dolaphenvaline. The derivatives of fragments and whole structures were evaluated for antifouling activity against the cypris larvae of Amphibalanus amphitrite. Small fragments inhibited the settlement of the cypris larvae at potent to moderate concentrations (EC50 = 0.60-4.62 mu g/mL), although dolastatin 16 with a substituent on the aromatic ring (24) was much less potent than dolastatin 16

Vogesella urethralis-induced aspiration pneumonia and bacteremia in an elderly man: a first case report and literature review

Abstract Background Vogesella species are common aquatic Gram-negative rods that were first reported in 1997. Vogesella urethralis bacterium was first isolated from human urine in 2020. Only two cases of disease caused by Vogesella species have been reported with no case of Vogesella urethralis-caused disease being reported as yet. Herein, we report a case of aspiration pneumonia and bacteremia caused by Vogesella urethralis. Case presentation An 82-year-old male patient was admitted with dyspnea, increased sputum production, and hypoxia. Gram-negative rods were isolated from the blood and sputum cultures of the patient. He was diagnosed with aspiration pneumonia and bacteremia. Initially, Vogesella urethralis was wrongly identified as Comamonas testosteroni based on fully automated susceptibility testing; however, additional 16S rRNA gene sequencing identified the causative as Vogesella urethralis. The patient was treated with piperacillin and tazobactam. Unfortunately, he developed aspiration pneumonia again and died during hospitalization. Conclusions Since no database exists for rare bacteria in traditional clinical microbiology laboratories, 16S rRNA gene sequence analysis is useful. We report the first case of Vogesella urethralis-induced aspiration pneumonia and bacteremia