Koen Peeters

Synthesis of 1-deoxymannojirimycin analogues using N-tosyl and N-nosyl activated aziridines derived from 1-amino-1-deoxyglucitol

Abstract 3,4;5,6-Diisopropylidene protected 1-amino-1-deoxy- d -glucitol was transformed into N -tosyl and N -nosyl activated aziridine intermediates, which underwent ring opening by reaction with various nucleophiles. The 5,6-diols resulting from selective hydrolysis of the terminal acetal group were subjected to (2-N→6-OH) cyclisation using two different methods for activation of 6-OH. Final deprotection of the N -nosyl and 3,4-acetal group proceeded smoothly to afford 6-substituted analogues of 1-deoxymannojirimycin.

The synthesis of 6-azido and 6-amino analogues of 1-deoxynojirimycin and their conversion to bicyclic derivatives

Abstract 1-Amino-1-deoxy- d -glucitol (14) was converted to the N-Boc-2,3;5,6-di-O-isopropylidene derivative 16 which was transformed further into the selectively protected 2,3-O-isopropylidene 6-azido piperidine 3. The synthesis proceeded via a double inversion at C-5 involving internal attack of 4-OH to form the 4,5-epoxide 28, and ring opening of this epoxide by 1-NH2 to generate the piperidine 3. This served as a valuable precursor of various target compounds, i.e. 6-azido- and 6-amino-1,6-dideoxynojirimycin 4 and 5, and the mono- and bicyclic derivatives 6–12.

Use of the N-tosyl-activated aziridine 1,2-dideoxy-1,2-iminomannitol as a synthon for 1-deoxymannojirimycin analogues

Abstract 1-Amino-1-deoxy- d -glucitol was converted into the selectively protected title compound 4, an N-tosyl-activated aziridine that readily underwent ring opening with various nucleophiles. Further deprotection of the 5,6-diol moiety followed by ring closure under Mitsunobu conditions afforded the corresponding 6-substituted analogues of 1-deoxymannojirimycin.

The synthesis of ester and ketone analogues of 1-deoxynojirimycin and castanospermine

Abstract 1-Amino-1-deoxy-D-glucitol (3) was converted into the 3,4;5,6-di-O-isopropylidene protected ammonium salt 17 which was transformed further into the trans-fused piperidine acetonides 4–8 in six steps and 23–32% overall yield. In the final step, ring closure was effected via cleavage of the N-Boc group of intermediates 27–29 with trimethylsilyl iodide: this enabled internal, face selective 1,4-addition of the free amino group to the (5,6)-α,β-unsaturated carbonyl moiety. Further modification and (or) deprotection of compounds 4–8 afforded the piperidine and indolizidine imino sugars 9–12 and 14–15.

An in vitro approach to the evaluation of foot-ankle kinematics: Performance evaluation of a custom-built gait simulator

Despite their well-known limitations, in vitro experiments have several benefits over in vivo techniques when exploring foot biomechanics under conditions characteristic of gait. In this study, we present a new setup for dynamic in vitro gait simulation that integrates a numerical model for generating the tibial kinematics control input, and we present an innovative methodology to measure full three-dimensional joint kinematics during gait simulations. The gait simulator applies forces to the tendons. Tibial kinematics in the sagittal plane is controlled using a numerical model that takes into account foot morphology. The methodology is validated by comparing joint rotations measured during gait simulation with those measured in vivo. In addition, reliability and accuracy of the control system as well as simulation input and output repeatability are quantified. The results reflect good control performance and repeatability of the control inputs, vertical ground reaction force, center of pressure displacement, and joint rotations and translations. In addition, there is a good correspondence to in vivo kinematics for most patterns of motion at the ankle, subtalar, and Chopart’s joints. Therefore, these results show the relevance and validity of including specimen-specific information for defining the control inputs.

Alterated Talar and Navicular Bone Morphology Is Associated with Pes Planus Deformity: A CT-Scan Study

We compared bone and articular morphology of the talus and navicular in clinically diagnosed flatfeet and evaluated their potential contribution to talo‐navicular joint instability. We used CT images to develop 3D models of talus and navicular bones of 10 clinically diagnosed flatfeet and 15 non‐flatfeet. We quantified their global bone dimensions, inclination and dimensions of the articular surfaces and their curvatures. Additionally, ratios of six talar and navicular dimensions were calculated. The values for these parameters were then compared between both groups. In flatfeet, the talar head faced more proximal and its width was larger compared to non‐flatfeet. Also the navicular cup faced more proximal and its depth was significantly increased. Furthermore, we observed a more protruding talar head compared to the navicular cup in the control group with the articular surface depth being relatively larger for the navicular cups when compared to the talus in flatfeet. The ratio of the talar and navicular articular surface height was decreased in flatfeet, suggesting increased height of navicular cups relative to the articulating talar heads. Our results show that flatfoot deformity is associated with morphological changes of talar and navicular articular surfaces that can favor medial arch collapse and forefoot abduction.

In vitro analysis of muscle activity illustrates mediolateral decoupling of hind and mid foot bone motion

Activity of the extrinsic ankle-foot muscles is typically described for the whole foot. This study determines if this muscle activity is also confirmed for individual foot segments defined in multi-segment foot models used for clinical gait analysis. Analysis of the individual bone motion can identify functional complexes within the foot and evaluates the influence of an altered foot position on muscle activity. A custom designed and built gait simulator incorporating pneumatic actuators is used to control the muscle force of six muscle groups in cadaveric feet. Measurements were performed in three static postures in which individual muscle force was incrementally changed. The motion of four bone embedded LED-clusters was measured using a Krypton motion capture system and resulting motion of calcaneus, talus, navicular and cuboid was calculated. Results indicate that primary muscle activity at bone level corresponds with that described for the whole foot. Secondary activity is not always coherent for bones within one segment: decoupling of the movement of medial and lateral foot bones is documented. Furthermore, secondary muscle activity can alter according to foot position. The observed medio-lateral decoupling of the foot bones dictates the need to extend some of the multi-segment foot models currently used in clinical gait analysis.

Specimen-specific tibial kinematics model for in vitro gait simulations

Until now, the methods used to set up in vitro gait simulations were not specimen specific, inflicting several problems when dealing with specimens of considerably different dimensions and requiring arbitrary parameter tuning of the control variables. We constructed a model that accounts for the geometric dimensions of the specimen and is able to predict the tibial kinematics during the stance phase. The model predicts tibial kinematics of in vivo subjects with very good accuracy. Furthermore, if used in in vitro gait simulation studies, it is able to recreate physiological vertical ground reaction forces. By using this methodology, in vitro studies can be performed by taking the specimen variability into account, avoiding pitfalls with specimens of different dimensions.

Design Considerations for Lateral Skin Stretch and Perpendicular Indentation Displays to Be Used in Minimally Invasive Surgery

Despite the advantages of minimally invasive surgery the applicability of (robot assisted) minimally invasive techniques is limited to simple operations due to the lack of tactile feedback. Tactile feedback is essential in many operations such as border detection during tumor resections and localization of nerves and veins embedded in soft tissue. This work compares the performance of existing tactile stimulation methods using psychophysical techniques in an edge detection test. Several mechanical and psychophysical design considerations for lateral skin stretch and perpendicular indentation displays are given. Considering the list of disadvantages, related to lateral skin stretch, we conclude that perpendicular indentation is the preferred stimulation method for tactile feedback systems to be used in minimally invasive surgery.

Inertial control: a novel technique for in-vitro analysis of foot function

Background In-vitro gait simulations have great potential, allowing a systematic analysis of the foot function. However, it is important that the loading conditions are realistic i.e. physiologic ground reaction forces (GRF). In most experiments, in-vivo measured GRF can be imposed [1,2]. However in experimental designs that evaluate the effect of altered muscle forces on foot motion this is more complex; the effect of the altered muscle activity on the loading and kinematics cannot be taken into consideration. Therefore, we investigated the use of a new technique to simulate such cases with realistic loading conditions.