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Background The high glycolytic activity of multiple myeloma (MM) cells is the rationale for use of Positron Emission Tomography (PET) with 18F-fluorodeoxyglucose ([18F]FDG) to detect both bone marrow (BM) and extramedullary disease. However, FDG-PET has some limitations, since there is a portion of MM patients who are negative, and new tracers are actively searched. Glutamine (Gln) addiction has been recently described as a peculiar metabolic feature of MM cells. Yet, the possible exploitation of Gln as a PET tracer in MM has never been assessed thus far and is investigated in this study. Methods We have firstly synthesized enantiopure (2S,4R)-4-fluoroglutamine (4-FGln) and validated it as a Gln transport analogue in human MM cell lines, comparing its uptake with that of 3H-labelled Gln. We then radiosynthesized of [18F]4-FGln and tested its uptake for MM detection by PET in two different murine models and we checked the effect of Bortezomib treatment. Results Both [18F]4-FGln and [18F]FDG clearly identified the spleen as site of MM cell colonization in C57BL/6 mice challenged with syngeneic Vk12598 cells and assessed by PET. NOD.SCID mice subcutaneously injected with human MM JJN3 cells, showed high values of both [18F]4-FGln and [18F]FDG uptake to T/M: 2.3 ± 0.3 and 7.1 ± 2.6, respectively. With both [18F]4-FGln and [18F]FDG radiotracers, BOR treated animals displayed Standard Uptake Values (SUV) mean values significantly lower than controls at post treatment PET. However, [18F]4-FGln better correlated with the tumour volume in NOD.SCID mice, and a reduction of glutaminolytic, but not of glycolytic, tumour volume was evident in mice showing the highest response to Bortezomib. Conclusion Our data indicate that [18F](2S,4R)-4-FGln is a new PET tracer in pre-clinical MM models, yielding a rationale to design studies in MM patients.

A practical, catalytic and enantioselective vinylogous Mukaiyama aldol reaction between 2-silyloxypyrrole donors and aromatic or heteroaromatic aldehyde acceptors is described. Using an enantiopure bisphosphoramide catalyst in conjunction with SiCl 4 , a variety of α,β-unsaturated-δ-hydroxylated γ-butyrolactam compounds were synthesized in high yields and with good to excellent levels of site-, diastereo- and enantioselectivity.

Novel hybrid porphyrins bearing two and four suitably protected glycosidic units appended at the meso positions of the central macrocycle through robust carbon–carbon bonds have been constructed and characterized. Metallation of these constructs with certain bivalent metal ions then produced a series of porphyrinato entities which had all the sugar protecting groups removed to arrive at the corresponding water soluble porphyrin–sugar hybrid species. It is noteworthy that two palladium derivatives, compounds 6 and 10 , proved to be efficient reagents for the selective cleavage of double strand DNA into form II nicked circular DNA upon exposure to visible light at room temperature in aqueous media.

The total synthesis of a potential inhibitor of HIV-protease—the chiral nonracemic six-membered hydroxy lactam 6 —has been accomplished, that involves, as key reaction, the highly diastereoselective vinylogous Mannich addition of furan-based silyloxy diene 7 to glyceraldeyde imine 8 .

trans-β-Hydroxypipecolic acids of both l - and d -series, l -1 and d -1, have been straightforwardly prepared in 14% and 15% yields, respectively, starting from glyceraldehyde imines d -7 and l -7 as useful three-carbon chirons. The key feature of these parallel syntheses lies on the highly diastereoselective character of the initial coupling manoeuver between silyloxy furan TBSOF and imines 7, which ultimately accounts for the relative, and hence absolute configuration of the target pipecolic acids.

A new efficient synthesis of 3-amino-3-deoxy- d -altrose (13), 3-amino-3-deoxy- l -allose (17), and 4-amino-4-deoxy- d -talose (21) from 2,3-O- isopropylidene- d -glyceraldehyde (6) using N-(tert-butoxycarbonyl)-2-(tert-butyldimethylsiloxy)pyrrole (TBSOP) as homologative nucleophile is described. The procedure highlights the merits of densely functionalized homochiral heptonolactam 9 as a key divergent intermediate.

Exploiting N-(tert-butoxycarbonyl)-2-(tert-butyldimethylsiloxy)pyrrole (TBSOP) as a masked glycine anion equivalent, a short enantiospecific synthesis of the title C-glycosyl α-aminoacid 5 was devised and executed, via diastereospecific α-C-glycosylation of protected arabinose 1 at the anomeric carbon.

Concise syntheses of two enantiomeric tetrahydroxyquinolizidines, 10 and ent-10, have been achieved from D-arabinose and L-arabinose, respectively. Highly diastereoselective homologation of imine 5 (or ent-5) using 2-(trimethylsiloxy)furan provided the nine-carbon butenolide 6 (or ent-6) which was elaborated into the quinolizidine 10 (or ent-10) via a clean sequence involving, as key operations, DBU-promoted γ-lactone to δ-lactam ring expansion (e.g. 7 to 8) and cyclodehydration of a fully-deprotected hydroxypiperidine employing Ph3P, CCl4, Et3N (e.g. 9 to 10). The procedure comprises five steps from 5 or ent-5 and provides the title quinolizidine 10 or its enantiomer ent-10 in 36–37% overall yields.

Stereochemically defined 4-amino-2,3,4-trideoxyaldonic acids 4 , representatives of a new progeny of C-glycosylated GABAs, have been synthesized from the readily available aldehydo precursors 1 in three steps and 60–75% overall yields. The key reaction is the SnCl 4 -assisted regio- and diastereoselective homologation of 1 with the nitrogen-containing five-membered ring siloxydiene TBSOP.