Oxetanes from the Ring Contraction of ?-Triflates of ?-Lactones: Oxetane Nucleosides and Oxetane Amino Acids

?-Triflates of ?-lactones with potassium carbonate in methanol give efficient contraction of the ring to oxetane-1-carboxylates in which the oxygen substituent at C(3) of the oxetane is predominantly trans to the carboxylate at C(2), regardless of the stereochemistry of the starting triflate. The limitations of the procedure are discussed and compared with analogous reactions for the preparation of THF carboxylates. The potential of the contraction in the preparation of oxetane nucleosides (such as oxetanocin) and oxetane sugar amino acids (analogues of oxetin) as peptidomimetics with predisposition to form secondary structural motifs is illustrated

Q: Is ketamine effective and safe for treatment-resistant depression?

Evidence-based answer: Maybe, but it’s too soon to tell. There is limited evidence that ketamine by itself is effective in the very short term. Single-dose intravenous (IV) ketamine is more likely than placebo (odds ratio = 11-13) to produce improvement (> 50%) in standardized depression scores in 1 to 3 days, lasting up to a week. Twice- or thriceweekly IV ketamine improves symptom scores by 20%-25% over 2 weeks (strength of recommendation [SOR]: B, meta-analysis of small, low-quality, randomized controlled trials [RCTs] and a single small RCT). Augmentation of sertraline with daily oral ketamine moderately improves symptom scores for 6 weeks in patients with moderate depression (SOR: B, small, low-quality RCTs). Augmentation of oral antidepressants (duloxetine, escitalopram, sertraline, venlafaxine) with intranasal esketamine spray improves response and remission rates at 4 weeks (16% for both outcomes) in patients with predominantly treatment-resistant major depression (SOR: A, meta-analysis of RCTs). Ketamine therapy is associated with confusion, emotional blunting, headache, dizziness, and blurred vision (SOR: A, meta-analyses). Nasal esketamine spray produces the adverse effects of dizziness, vertigo, and blurred vision severe enough to cause discontinuation in 4% of patients; it also can produce transient elevation of blood pressure (SOR: A, meta-analyses).Amanda Zorn, MD; Sean Linn, PharmD; Mat Jenkinson, PharmD; Jon O. Neher, MD (Valley Family Medicine, Residency, University of Washington at Valley, Renton), Sarah Safranek, MLIS (Health Sciences Librarian Emeritus, University of Washington Medical School, Seattle)Includes bibliographical reference

2-De­oxy-2,3-O-isopropyl­idene-2,4-di-C-methyl-β-l-arabinose

X-ray crystallography unequivocally confirmed the stereochemistry of the C atom at position 2 in the carbon scaffold of the title mol­ecule, C10H18O4. The pyran­ose ring exists in a chair conformation with the methyl group on the C atom in the 2 position in an equatorial configuration. The absolute stereochemistry was determined from the starting material. The crystal structure consists of O—H⋯O hydrogen-bonded chains of mol­ecules running parallel to the b axis

2,3-O-(S)-Benzyl­idene-2-C-methyl-d-ribono-1,4-lactone

The crystal structure of the title compound, C13H14O5, establishes (i) the (S) – rather than (R) – configuration at the acetal carbon and (ii) that both the acetal and the lactone form five- rather than six-membered rings; the absolute configuration is determined by the use of 2-C-methyl-d-ribono-1,4-lactone as the starting material. The compound consists of hydrogen-bonded chains of mol­ecules running along the a axis; there are no unusual packing features. Only classical hydrogen bonding has been considered

Synthesis and Biological Evaluation of Amidinourea and Triazine Congeners as Inhibitors of MDA-MB-231 Human Breast Cancer Cell Proliferation

A series of novel amidinourea derivatives has been synthesised and the new compounds have been evaluated as inhibitors of MDA-MB-231 human breast cancer cell proliferation. In addition, a second series of triazine derivatives designed as rigid congeners of the amidinoureas was synthesised as well and the compounds were evaluated for their antiproliferative activity. Among the two series, the amidinourea 3d emerged as a potent anticancer hit compound with IC50 = 0.76 micormolar comparable to tamoxifen

(4R)-4-(2-Allyl-2H-1,2,3-triazol-4-yl)-1,2-O-isopropyl­idene-l-threose

X-ray crystallography unequivocally confirmed the structure of the title compound, C12H17N3O4, as (4R)-4-(2-allyl-2H-1,2,3-triazol-4-yl)-1,2-O-isopropyl­idene-l-threose. The absolute configuration was determined by the use of d-glucorono-3,6-lactone as the starting material. The crystal structure consists of hydrogen-bonded chains of mol­ecules running parallel to the a axis. There are no unusual packing features

tert-Butyl 2-de­oxy-4,5-O-isopropyl­idene-d-gluconate

The relative configuration of tert-butyl 2-de­oxy-4,5-O-iso­propyl­idene-d-gluconate, C13H24O6, an inter­mediate in the synthesis of 2-de­oxy sugars, was determined by X-ray crystallography, and the crystal structure consists of chains of O—H⋯O hydrogen-bonded mol­ecules running parallel to the a axis. There are two mol­ecules in the asymmetric unit. The absolute configuration was inferred from the use of d-erythrono­lactone as the starting material

(4S,5R,6R)-Methyl 4-hydr­oxy-4,5-iso­propyl­idenedioxy-4,5,6,7-tetra­hydro-1,2,3-triazolo[1,5-a]pyridine-3-carboxyl­ate. Erratum

Corrigendum to Acta Cryst. (2009), E65, o610–o611