Enantioselective Syntheses of Lignin Models: An Efficient Synthesis of ß-O-4 Dimers and Trimers by Using the Evans Chiral Auxiliary.

We describe an efficient five-step, enantioselective synthesis of (R,R)- and (S,S)-lignin dimer models possessing a ß-O-4 linkage, by using the Evans chiral aldol reaction as a key step. Mitsunobu inversion of the (R,R)- or (S,S)-isomers generates the corresponding (R,S)- and (S,R)-diastereomers. We further extend this approach to the enantioselective synthesis of a lignin trimer model. These lignin models are synthesized with excellent ee (>99 %) and high overall yields. The lignin dimer models can be scaled up to provide multigram quantities that are not attainable by using previous methodologies. These lignin models will be useful in degradation studies probing the selectivity of enzymatic, microbial, and chemical processes that deconstruct lignin.

Tailored near-infrared contrast agents for image guided surgery.

The success of near-infrared (NIR) fluorescence to be employed for intraoperative imaging relies on the ability to develop a highly stable, NIR fluorescent, nontoxic, biocompatible, and highly excreted compound that retains a reactive functionality for conjugation to a cancer-recognizing peptide. Herein, systematic modifications to previously detailed fluorophore ZW800-1 are explored. Specific modifications, including the isosteric replacement of the O atom of ZW800-1, include nucleophilic amine and sulfur species attached to the heptamethine core. These novel compounds have shown similar satisfactory results in biodistribution and clearance while also expressing increased stability in serum. Most importantly, all of the synthesized and evaluated compounds display a reactive functionality (either a free amino group or carboxylic acid moiety) for further bioconjugation. The results obtained from the newly prepared derivatives demonstrate that the central substitution with the studied linking agents retains the ultralow background in vivo performance of the fluorophores regardless of the total net charge.

Synthesis of enantiomerically pure lignin dimer models for catalytic selectivity studies.

A series of highly enantioselective transformations, such as the Sharpless asymmetric epoxidation and Jacobsen hydrolytic kinetic resolution, were utilized to achieve the complete stereoselective synthesis of ß-O-4 lignin dimer models containing the S, G, and H subunits with excellent ee (>99%) and moderate to high yields. This unprecedented synthetic method can be exploited for enzymatic, microbial, and chemical investigations into lignin's degradation and depolymerization as related to its stereochemical constitution. Preliminary degradation studies using enantiopure Co(salen) catalysts are also reported.

Prototype nerve-specific near-infrared fluorophores.

Nerve preservation is an important issue during most surgery because accidental transection or injury results in significant morbidity, including numbness, pain, weakness, or paralysis. Currently, nerves are still identified only by gross appearance and anatomical location during surgery, without intraoperative image guidance. Near-infrared (NIR) fluorescent light, in the wavelength range of 650-900 nm, has the potential to provide high-resolution, high-sensitivity, and real-time avoidance of nerve damage, but only if nerve-specific NIR fluorophores can be developed. In this study, we evaluated a series of Oxazine derivatives to highlight various peripheral nerve structures in small and large animals. Among the targeted fluorophores, Oxazine 4 has peak emission near into the NIR, which provided nerve-targeted signal in the brachial plexus and sciatic nerve for up to 12 h after a single intravenous injection. In addition, recurrent laryngeal nerves were successfully identified and highlighted in real time in swine, which could be preserved during the course of thyroid resection. Although optical properties of these agents are not yet optimal, chemical structure analysis provides a basis for improving these prototype nerve-specific NIR fluorophores even further.