A New Synthesis of Enantiopure Amine Fragment: An Important Intermediate to the Anti-HIV Drug Lenacapavir.

Herein, we describe a new seven-step approach to prepare ()-1-(3,6-dibromopyridin-2-yl)-2-(3,5-difluorophenyl)ethan-1-amine (()-) from the inexpensive 2-(3,5-difluorophenyl)acetic acid. The key steps in the sequence include (1) the Weinreb amide-based ketone synthesis to provide an entry point to the core structure; (2) simple functional group transformations to afford the racemic amine -; and (3) dynamic kinetic resolution (DKR) to access the chiral amine ()-. This seven-step process delivered the enantiopure amine ()- in an overall isolated yield of approximately 15%.

Practical Synthesis of 7-Bromo-4-chloro-1-indazol-3-amine: An Important Intermediate to Lenacapavir.

7-Bromo-4-chloro-1-indazol-3-amine is a heterocyclic fragment used in the synthesis of Lenacapavir, a potent capsid inhibitor for the treatment of HIV-1 infections. In this manuscript, we describe a new approach to synthesizing 7-bromo-4-chloro-1-indazol-3-amine from inexpensive 2,6-dichlorobenzonitrile. This synthetic method utilizes a two-step sequence including regioselective bromination and heterocycle formation with hydrazine to give the desired product in an overall isolated yield of 38-45%.

Highly Regioselective Protecting-Group-Free Synthesis of the Antimalarial Drug MMV693183.

MMV693183 is a promising antimalarial drug candidate that works for uncomplicated malaria treatment and resistance management. Herein, we report an efficient and highly regioselective synthesis of MMV693183. This novel synthetic method highlights a three-step route with an overall yield of 46% from readily available starting materials.

Effect of Tibial Tunnel Placement Using the Lateral Meniscus as a Landmark on Clinical Outcomes of Anatomic Single-Bundle Anterior Cruciate Ligament Reconstruction.

Background: It remains unclear if use of the lateral meniscus anterior horn (LMAH) as a landmark will produce consistent tunnel positions in the anteroposterior (AP) distance across the tibial plateau.

Purpose: To evaluate the AP location of anterior cruciate ligament (ACL) reconstruction tibial tunnels utilizing the LMAH as an intra-articular landmark and to examine how tunnel placement affects knee stability and clinical outcomes.

Study Design: Cohort study; Level of evidence, 3.

Allograft Bone Dowels Show Better Incorporation in Femoral Versus Tibial Tunnels in 2-Stage Revision Anterior Cruciate Ligament Reconstruction: A Computed Tomography-Based Analysis.

Purpose: The purpose of this study was to quantitatively evaluate the radiographic outcomes of allograft dowels used in 2-stage revision anterior cruciate ligament reconstruction (ACLR) and to compare the incorporation rates of dowels placed in tibial and femoral tunnels.

Methods: Prospective review of patients who underwent 2-stage revision ACLR with allograft bone dowels. Inclusion criteria were tibial/femoral tunnel diameter of ≥14 mm on preoperative computed tomography (CT) or overlapping of prior tunnels with planned tunnels.

Etiology of Shoulder Arthritis in Young Patients.

The manifestation of glenohumeral arthritis in the young adult is a devastating occurrence that can be difficult to manage. This review details the many underlying etiologies including genetic causes, congenital abnormalities, glenohumeral instability, posttraumatic lesions, postcapsulorraphy arthropathy, osteonecrosis, intraarticular pain pump postoperative use, radiofrequency/thermal capsulorraphy treatments, septic arthritis/infection, and inflammatory arthropathies. Although each of these potential causes have been well-studied, their contributions to the development of glenohumeral arthritis in the young person has not been described extensively.

Surgical Management of the Multiple-Ligament Knee Injury.

The management of multiligament knee injury is a complex process starting with the adequate identification of the injury. A detailed physical and radiographic examination with a thorough understanding of knee anatomy is crucial to assess all damaged structures: anterior cruciate ligament, posterior cruciate ligament, posteromedial corner including the medial collateral ligament, and posterolateral corner including the lateral collateral ligament. Several surgical techniques have been developed throughout the years to adequately address these ligament insufficiencies.

Sulcus-Deepening Trochleoplasty and Medial Patellofemoral Ligament Reconstruction for Recurrent Patellar Instability.

There are multiple etiologies for recurrent patellar instability. While patella alta, an elevated tibial tubercle trochlear groove distance, and prior lateral patellar dislocations with medial patellofemoral ligament (MPFL) insufficiency have been shown to be risk factors for recurrent patellar instability, trochlear dysplasia can result in a significant impediment to normal patellar tracking. With the adequate identification of risk factors, appropriate surgical treatments can be individually tailored to the patient.

Circumferential Suture Repair of Isolated Horizontal Meniscal Tears Augmented With Fibrin Clot.

Traditionally, horizontal cleavage meniscus tears have been associated with osteoarthritis, indicative of the degenerative process. Recent treatment measures have focused on maintaining as much meniscal tissue as possible, despite the routine extension of these tears into the central white-white zones. In the absence of tunnel drilling for cruciate ligament reconstructions, the use of an exogenous fibrin clot is a useful adjunct to increase the local growth factors at the tear repair to aid in healing.

Meniscal Ramp Lesion Repair by a Trans-septal Portal Technique.

The identification of meniscal ramp lesions can be quite difficult or even impossible with conventional anterior arthroscopic viewing and working portals. Although even the use of transnotch viewing maneuvers into the posteromedial compartment increases the likelihood of diagnosis, it is the posteromedial and trans-septal portals that provide the best direct visualization of these many times "hidden lesions." In this surgical technique description, we describe a method to not only adequately visualize the ramp lesion, but also provide subtle variations to existing surgical techniques that can help limit injury to neurovascular structures as well as gain satisfactory vertical suture repair of this posteromedial meniscocapsular injury.

Two-Stage Revision Anterior Cruciate Ligament Reconstruction Using Allograft Bone Dowels.

Revision anterior cruciate ligament (ACL) reconstruction is substantially more challenging than primary reconstruction. Management of previously malpositioned or widened tunnels often requires innovative approaches for managing bony defects. Massive osteolysis with poor bone stock and convergence or overlapping of revision tunnels into the previously placed tunnels may necessitate a staged revision procedure.

Current Concepts in the Management of Patellar Instability.

Patellar instability is a common presenting clinical entity in the field of orthopedics. This not only can occur from baseline morphologic variability within the patellofemoral articulation and alignment, but also from traumatic injury. While conservative management is many times employed early in the treatment course, symptomatic patellar instability can persist.

Invasive Compartment Pressure Testing for Chronic Exertional Compartment Syndrome: A Survey of Clinical Practice Among Military Orthopedic Surgeons.

We surveyed military orthopedic surgeons to investigate the clinical practice of performing invasive compartment pressure (ICP) testing in patients with suspected chronic exertional compartment syndrome (CECS).Eighty-five percent of respondents agreed or strongly agreed with always confirming the diagnosis of CECS with ICP testing. Thirty-nine percent stated they would recommend surgical treatment without ICP testing if they were confident about the diagnosis based on clinical examination findings.

140 H/D isotopomers identified by long-range NMR hyperfine shifts in ruthenium(III) ammine complexes. Hyperconjugation in Ru-NH3 bonding.

(1)H NMR spectra of the paramagnetic cyanide-bridged mixed-valence compound [(η(5)-C5H5)Fe(CO)2(μ-CN)Ru(NH3)5](CF3SO3)3 (I) have been obtained in several solvents. When traces of partially deuterated water are present, instead of a single cyclopentadienyl (Cp) resonance shifted by the hyperfine interaction, numerous well-resolved resonances are observed. The spectra were simulated satisfactorily by giving the appropriate statistical weight to 140 possible H/D isotopomers formed by deuteration in the five ruthenium(III) ammine ligands.

Proximal tibiofibular joint pain after insertion of a tibial intramedullary nail: two case reports with accompanying computed tomography and cadaveric studies.

Intramedullary nail (IMN) fixation is a proven, efficient, and effective surgical intervention for diaphyseal tibia fractures. We present a case report of two patients who sustained diaphyseal tibial fractures, were treated with IMN fixation, and subsequently developed lateral and posterolateral knee pain secondary to interlocking screw penetration into the proximal tibiofibular joint (PTFJ). We performed a retrospective radiographic review of 50 consecutive knee computed tomographic scans to define the fibula's respective anatomic relationship to the tibia on axial computed tomographic images in addition to a cadaveric study of four IMN implants to evaluate the orientation of the medial inserted proximal oblique interlock screw with three-dimensional reconstructive fluoroscopy.

Assessment of tibiofemoral position in total knee arthroplasty using the active flexion lateral radiograph.

This study is a retrospective comparative cohort radiographic analysis of 114 consecutive patients who underwent posterior cruciate retaining (PCR) total knee arthroplasty (TKA), medial and patellofemoral compartment bicruciate retaining arthroplasty (BCR), or bicruciate substituting (BCS) TKA. In an effort to obtain a quantitative measurement of both anteroposterior (AP) tibiofemoral position and active knee flexion we have routinely taken post-operative lateral radiographs in a position of maximal active flexion. Passive range of motion (PRoM) after TKA was significantly greater than pre-operative passive range of motion for each cohort (p<0.

Cyanide (13)C NMR hyperfine shifts in paramagnetic cyanide-bridged mixed-valence complexes.

Paramagnetic (hyperfine) NMR shifts in the (13)C cyanide bridge and (31)P resonances in a set of mixed valence complexes [(eta(5)-C(5)R(5))Ru(PPh(3))L((13)CN)Ru(NH(3))(5)](n+) (R = H; L = PPh(3), CO, NO(+); R = Me; L = PPh(3)) are sensitive to the extent of intermetallic charge-transfer, and are strongly solvent dependent.