Effects of hemoglobin level on the early postsurgical cerebral metabolism in patients with severe traumatic brain injury.

OBJECTIVE: The study aims to explore the effects of different levels of haemoglobin (Hb) on early cerebral metabolism in patients with postoperative severe traumatic brain injury (TBI) . METHOD: Fifty-nine patients were randomly divided into catheter oxygen group and ventilator-assisted respiratory group. Each group was subsequently divided into three subgroups basing on different Hb level: Hb ≤ 70 g/L subgroup, 71 g/L ≤ Hb≤90 g/L subgroup and Hb ≥ 91 g/L subgroup. The blood samples from the femoral artery and the affected side internal jugular vein were, respectively, taken at the same time from the patient after postoperative 3 days. RESULTS: The incidence of anaemia after severe TBI operation was 88.14%. The VADL and cerebral glucose uptake (CMRglu) in both Hb ≤ 70 g/L and 71 g/L ≤ Hb≤90 g/L patients of oxygen catheter group were less than that in Hb ≥ 91 g/L patients. In the ventilator-assisted breathing group, the VADL and CMRglu of 71 g/L ≤ Hb≤90 g/L patients and Hb ≥ 91 g/L patients were lower than those in Hb ≤ 70 g/L patients. The result from comparing the two 71 g/L ≤ Hb ≤ 90 g/L subgroups showed that the brain metabolic indexs in the ventilator-assisted breathing group were better than those in the catheter oxygen group. CONCLUSIONS: In severe TBI postoperative patients, Hb≤90 g/L induced decrease in aerobic oxidation in brain tissue. Moreover, for the same Hb level of 71 g/L ≤ Hb≤90 g/L, ventilator-assisted breathing significantly improved cerebral metabolism.

General one-pot reductive gem-bis-alkylation of tertiary lactams/amides: rapid construction of 1-azaspirocycles and formal total synthesis of (±)-cephalotaxine.

Amides are a class of highly stable and readily available compounds. The amide functional group constitutes a class of powerful directing/activating and protecting group for C-C bond formation. Tertiary tert-alkylamine, including 1-azaspirocycle is a key structural feature found in many bioactive natural products and pharmaceuticals. The transformation of amides into tert-alkylamines generally requires several steps. In this paper, we report the full details of the first general method for the direct transformation of tertiary lactams/amides into tert-alkylamines. The method is based on in situ activation of amide with triflic anhydride/2,6-di-tert-butyl-4-methylpyridine (DTBMP), followed by successive addition of two organometallic reagents of the same or different kinds to form two C-C bonds. Both alkyl and functionalized organometallic reagents and enolates can be used as the nucleophiles. The method displayed excellent 1,2- and good 1,3-asymmetric induction. Construction of 1-azaspirocycles from lactams required only two steps or even one-step by direct spiroannelation of lactams. The power of the method was demonstrated by a concise formal total synthesis of racemic cephalotaxine.

Asymmetric vinylogous Mannich reactions: a versatile approach to functionalized heterocycles.

Asymmetric vinylogous Mannich reaction (VMR) of 2-(tert-butyldimethylsilyloxy)furan (TBSOF, 1) with (R(S))- or (S(S))-t-BS-imines (3) furnished 5-aminoalkylbutenolides 7a-k in 75-87% yields with anti/syn ratios ranging from 75:25 to 97:3. Butenolides 7a-f,k were readily converted into substituted lactones 8 and 5 and 6-substituted 5-hydroxypiperidin-2-ones 11a-g, which are, in turn, key intermediates for the synthesis of many bioactive compounds.

Asymmetric syntheses and Wnt signal inhibitory activity of melleumin A and four analogues of melleumins A and B.

Guided by nature: A flexible and epimerization-free approach for the asymmetric syntheses of melleumin A and four analogues of melleumins A and B was developed, which allowed confirming the stereochemistry at C-4 of melleumin A, and revealed that the unnatural 4-epi-melleumin B possesses a modest inhibitory activity on Wnt signaling. The first total synthesis of melleumin A and four analogues of melleumins A and B is described. The N-acyl L-Thr-Gly/beta-hydroxy-gamma-amino acid coupling/macrolactamization strategy allowed the efficient assembly of the three segments being free of epimerization. While the Jouin-Castro method with minor modification allows a rapid entrance to the key syn-beta-hydroxy-gamma-amino acid segment, required for the synthesis of melleumin A, an extension of our malimide-based methodology using a changed N-protecting group affords a flexible access to several anti-beta-hydroxy-gamma-amino acids, and hence analogues of melleumins A and B. Among them, unnatural 4-epi-melleumin B (2 a) exhibits a modest inhibitory activity on Wnt signaling. The total synthesis of melleumin A allowed confirmation of its full structure.