A highly diastereoselective silver-catalysed cyclisation of a 2-substituted b-allenic hydroxylamine is reported. The resulting trans-isoxazolidine is converted into two Nuphar alkaloids by a sequence involving cross-metathesis and intramolecular reductive amination.
Background
Knee osteoarthritis (OA) is a leading cause of disability among older adults. Medical and surgical treatments are costly and associated with side effects. A natural nutraceutical, collagen hydrolysate, has received considerable attention due to its relieving effects on OA-associated symptoms. This study investigated the effects of hydrolyzed collagen type II (HC-II) and essence of chicken (BRAND'S Essence of Chicken) with added HC-II (EC-HC-II) on joint, muscle, and bone functions among older adults with OA.
Methods
Patients (n = 160) with grade 1–3 knee OA according to the Kellgren–Lawrence classification system, joint pain for ≥ 3 months, and a Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score of > 6 were randomly assigned with equal probability to consume EC-HC-II, HC-II, glucosamine HCl, or a placebo for 24 weeks in combination with resistance training. Outcome measurements were WOMAC score, visual analogue scale (VAS) pain score, grip strength, fat-free mass (FFM), and bone mass.
Results
All groups exhibited similar levels of improvement in WOMAC index scores after 24 weeks. HC-II significantly reduced VAS pain score by 0.9 ± 1.89 (p = 0.034) after 14 days. A repeated-measures analysis of variance showed that HC-II reduced pain levels more than the placebo did (mean ± standard error: − 1.3 ± 0.45, p = 0.021) after 14 days; the EC-HC-II group also had significantly higher FFM than the glucosamine HCl (p = 0.02) and placebo (p = 0.017) groups and significantly higher grip strength than the glucosamine HCl group (p = 0.002) at 24 weeks.
Conclusion
HC-II reduces pain, and EC-HC-II may improve FFM and muscle strength. This suggests that EC-HC-II may be a novel holistic solution for mobility by improving joint, muscle, and bone health among older adults. Large-scale studies should be conducted to validate these findings.
Trial registration
This trial was retrospectively registered at ClinicalTrials.gov (NCT04483024).
(À)-Deoxynupharidine has been synthesised via an intermediate that can also be used for other Nuphar alkaloids. Significants teps include the optimisede nzymatic resolution of an allenic alcohol, highly diastereoselective silvercatalysed cyclisation of an allenic hydroxylamine, selective cross-metathesis,d iastereoselectivei ntramolecular reductive amination,a nd stereoelectronically controlled enolate alkylation.
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