ABSTRACT
Detrimental biofilms of bacterial pathogens cause chronic infections with a high-level tolerance to antibiotics. To identify new control agents, we synthesized and tested a total of 14 tetronamides (including 5 new compounds) and 6 denigrin intermediates on the model species Escherichia coli. At a concentration of 50 µg/mL, two tetronamides and two methylated denigrins exhibited significant inhibitory effects against biofilm formation of E. coli RP437, e.g., by 60 and 94%, respectively. Structural analysis of the tested compounds revealed that p-methoxybenzylidene and p-methoxyphenethyl moieties of denigrins are important for biofilm inhibition, while the former group is also essential to the activity against quorum sensing (QS) via AI-2. Specifically, tetramethyldenigrin B has strong inhibitory effects against both E. coli biofilm formation and AI-2-mediated QS and thus provides a promising lead structure for designing better control agents. Consistently, tetramethyldenigrin B also showed inhibitory activity against biofilm formation of uropathogenic E. coli. Together, these findings provide new insights for the rational design of novel biofilm and QS inhibitors.
ABSTRACT
The first synthesis of enhygrolide A, a scarce γ-alkylidenebutenolide antibiotic of the obligate marine myxobacterium Enhygromyxa salina, was achieved in five steps and 54% overall yield from tetronic acid. Key steps include (i) organocatalytic reductive alkylation, (ii) iron-catalyzed sp2-sp3 cross-coupling, and (iii) vinylogous aldol condensation. Aside from its brevity and reliance on environmentally sustainable processes, the synthesis demonstrates the serviceability of butenolide pivalates in cross-coupling reactions.
Subject(s)
4-Butyrolactone/analogs & derivatives , Anti-Bacterial Agents/chemical synthesis , Benzylidene Compounds/chemical synthesis , Myxococcales/chemistry , 4-Butyrolactone/chemical synthesis , 4-Butyrolactone/chemistry , 4-Butyrolactone/pharmacology , Aldehydes/chemistry , Alkylation , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Benzylidene Compounds/chemistry , Benzylidene Compounds/pharmacology , Catalysis , Marine Biology , Molecular Structure , StereoisomerismABSTRACT
The first synthesis of the tetronamide antibiotic basidalin was accomplished in five steps and 39% overall yield from readily available 4-bromo-2-triisopropylsilyloxyfuran and 2-formyl-1,3-dithiane. Highlights include: (i) regio- and stereocontrolled assemblage of a pivotal (Z)-γ-ylidene-ß-bromobutenolide intermediate by stereodirected vinylogous aldol condensation (SVAC), (ii) installation of the amino group via aza-Michael addition/elimination, and crucially (iii) facile access to basidalin by late-stage dithiane removal.
Subject(s)
Antibiotics, Antineoplastic/chemistry , Antibiotics, Antineoplastic/chemical synthesis , Polyketides/chemistry , Aldehydes/chemistry , Furans/chemical synthesis , Furans/chemistry , Magnetic Resonance Spectroscopy , Molecular Structure , Quinolizines/chemistry , Stereoisomerism , Sulfur Compounds/chemistryABSTRACT
A stereoselective vinylogous aldol reaction of N-monosubstituted tetronamides with aldehydes is described. The procedure is simple and scalable, works well with both aromatic and aliphatic aldehydes, and affords mainly the corresponding syn-aldol adducts. In many cases, the latter are obtained essentially free of their anti-isomers (dr > 99 : 1) in high yields (70-90%). Experimental and computational studies suggest that the observed diastereoselectivity arises through anti-syn isomer interconversion, enabled by an iterative retro-aldol/aldol reaction.
ABSTRACT
Traditional open surgery has historically been the standard approach to treating many head and neck conditions. The introduction of the first robot into the surgical world in 1985 has been a keystone in the development of minimally invasive surgical (MIS) techniques. Transoral robotic surgery (TORS) is a minimally invasive technique used for the treatment of head and neck pathologies, including benign and malignant lesions. When performed in select patients, TORS offers low post-operative morbidity, along with very few functional and cosmetic compromises. Herein, we present the first TORS supraglottic partial laryngectomy performed in Puerto Rico or in any region in Latin America. A 68-year-old male who had previously undergone radiation therapy presented with hoarseness and weight loss. A suspension microlaryngoscopy showed a lesion of the left false vocal cord; a biopsy was performed. The patient was diagnosed with a supraglottic squamous cell carcinoma (T2N0M0); the tumor was completely excised using TORS. No post-operative complications occurred.
Subject(s)
Carcinoma, Squamous Cell/surgery , Head and Neck Neoplasms/surgery , Laryngeal Neoplasms/surgery , Laryngectomy/methods , Robotics/methods , Aged , Biopsy , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/pathology , Glottis , Head and Neck Neoplasms/diagnosis , Head and Neck Neoplasms/pathology , Humans , Laryngeal Neoplasms/diagnosis , Laryngeal Neoplasms/pathology , Laryngoscopy/methods , Male , Puerto Rico , Salvage Therapy/methods , Squamous Cell Carcinoma of Head and NeckABSTRACT
Urachal Cyst pathologies comprise lesions that arise at the medial infraumblical line which is rarely seen in an adult. It has interesting and varied forms of clinical presentations which represent a diagnostic challenge for the clinician. Persistency of the Urachus is due to failure of the normal obliteration process which occurs embriologically during the 4th gestational month. This gives way to a lesion that should be taken into account while considering the differential diagnoses of the cystic pathologies of the region. We present the case of an adult woman with a Urachal Cyst, which was surgically excised at the Hospital Interamericano de Medicina Avanzada in Caguas, Puerto Rico, followed by a brief literature review.
