Mobile point-of-care MRI demonstration of a normal volunteer in a telemedicine-equipped ambulance.

OBJECTIVE: Several centers have implemented ambulances equipped with CT scanners and telemedicine capabilities, known as mobile stroke units (MSU), to expedite acute stroke care delivery in the pre-hospital setting. While MSUs have been shown to improve outcomes compared with standard emergency medical management, there are limitations to incorporating CT, including radiation exposure to emergency medical services personnel. Recently, a portable, low-field strength MRI (Swoop®, Hyperfine, Inc., Guilford, CT) received FDA clearance for in-hospital use. Here, as proof-of-concept, we explore the possibility of performing MRI in a telemedicine-equipped ambulance during active transport. MATERIALS AND METHODS: In this initial technical demonstration, we imaged an MR phantom and a normal human volunteer using a standard stroke protocol during active ambulance transport. RESULTS: Images of the MR phantom and volunteer were successfully obtained and were immediately available for viewing in the hospital PACS system. The images were deemed of diagnostic quality by the radiologist. Active motion correction maintained superior image quality despite vehicle and scanner motion. In-plane, low contrast resolution of greater than 4 × 4 mm was achieved. Average transmit speeds were calculated to be 3.54 Megabits/second and upload data rates varied while in transit ranging from 8.54 to 4.13 Megabits/second. CONCLUSION: While MRI is not yet ready for clinical use in the MSU setting, our initial experience suggests potential technological feasible of this approach following future technical and MRI sequence development. Additional studies, incorporating patients, would be required to determine clinical feasibility.

Mechanistic Studies on the Base-Promoted Ring Opening of Glycal-Derived gem-Dibromocyclopropanes.

In the presence of a nucleophilic base, ring-fused gem-dibromocyclopropanes derived from d-glycals undergo ring opening to give 2-deoxy-2-(E-bromomethylene)glycosides. Such cleavage of an exocyclic cyclopropane bond contrasts with the more usual silver-promoted ring-expansion reactions in which endocyclic bond cleavage occurs. Experimental and theoretical studies are reported which provide insights into the reaction mechanism and the origin of its kinetic selectivity for E-configured bromoalkene products. Density functional theory computations (M06-2X) predict that the reaction commences with alkoxide-induced HBr elimination from the dibromocyclopropane to form a bromocyclopropene. Ring opening then gives a configurationally stable zwitterionic (oxocarbenium cation/vinyl carbanion) intermediate, which undergoes nucleophilic addition and protonation to give the bromoalkene. There are two competing sources of the proton in the final step: One is the alcohol (co)solvent, and the other is the molecule of alcohol produced during the initial deprotonation step. The roles of the formed alcohol molecule and the bulk (co)solvent are demonstrated by isotope-labeling studies performed with deuterated solvents. The acid-promoted isomerization of the E-bromoalkene product into the corresponding Z-bromoalkene is also described. The mechanistic knowledge gained in this investigation sheds light on the unusual chemistry of this system and facilitates its future application in new settings.

Synthesis of the (-)-TAN-2483B ring system via a D-mannose-derived cyclopropane.

The ring system of the fungal metabolite (-)-TAN-2483B has been synthesised, for the first time, from d-mannose, utilising a cyclopropanation/ring expansion sequence.

Synthesis of oxepines and 2-branched pyranosides from a d-glucal-derived gem-dibromo-1,2-cyclopropanated sugar.

The conversion of cyclopropane-fused carbohydrates into oxepines is an attractive method for accessing diverse members of the septanoside family of carbohydrate mimetics. 2-Bromooxepines are obtained through silver(I)-promoted thermal ring expansion of a d-glucal-derived gem-dihalocyclopropanated sugar. In contrast, cyclopropane ring cleavage under basic conditions leads to 2-C-branched pyranosides, not the 2-bromooxepine structures assigned in an earlier report.

Total Synthesis and Bioactivity Studies of Fungal Metabolite (-)-TAN-2483B.

The first total synthesis of (-)-TAN-2483B, a fungal metabolite possessing a densely functionalized furo[3,4-b]pyran-5-one framework, is achieved in 14 steps from d-mannose. Generation of the 2,6-trans-pyran is by cyclopropane ring expansion followed by α-selective alkynylation. Julia-Kocienski olefination introduces the E-propenyl side chain. Alkyne functionalization and carbonylation stereoselectively establish the bicyclic core of (-)-TAN-2483B. Inhibition of kinases Btk and Bmx, bacterial priority pathogens, and cytokine production in splenocytes indicates promising therapeutic potential.

Norborn-2-en-7-ones as physiologically-triggered carbon monoxide-releasing prodrugs.

A prodrug strategy for the release of the gasotransmitter CO at physiological pH, based upon 3a-bromo-norborn-2-en-7-one Diels-Alder cycloadducts of 2-bromomaleimides and 2,5-dimethyl-3,4-diphenylcyclopentadienone has been developed. Examples possessing protonated amine and diamine groups showed good water solubility and thermal stability. Half-lives for CO-release in TRIS-sucrose buffer at pH 7.4 ranged from 19 to 75 min at 37 °C and 31 to 32 h at 4 °C. Bioavailability in rats was demonstrated by oral gavage and oCOm-21 showed a dose dependent vasorelaxant effect in pre-contracted rat aortic rings with an EC50 of 1.6 ± 0.9 µM. Increased intracellular CO levels following oCOm-21 exposure were confirmed using a CO specific fluorescent probe.

Synthesis of C-furanosides from a D-glucal-derived cyclopropane through a ring-expansion/ring-contraction sequence.

gem-Dibromocyclopropane 1, prepared from tri-O-benzyl-D-glucal, undergoes thermal and silver-promoted ring expansion in the presence of alcohols to give substituted oxepines. With further heating, ring contraction to highly substituted tetrahydrofurans follows. These represent C-furanosides, potentially useful as precursors to C-nucleosides and other carbohydrate mimics.