| 1. |
- Carlsson, Anna-Carin, 1976, et al.
(författare)
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Microwave-assisted synthesis of the Schollkopf chiral auxiliaries: (3S)- and (3R)-3,6-dihydro-2,5-diethoxy-3-isopropyl-pyrazine
- 2006
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Ingår i: Tetrahedron Letters. - : Elsevier BV. - 0040-4039. ; 47:29, s. 5199-5201
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Tidskriftsartikel (refereegranskat)abstract
- A practical and efficient methodology for the laboratory scale preparation of Schollkopf's bis-lactim ether chiral auxiliaries (3S)- and (3R)-3,6-dihydro-2,5-diethoxy-3-isopropyl-pyrazine has been developed. The key step is the preparation of the 2,5diketopiperazine derivative by microwave-assisted heating in water. The protocol avoids reactions at low temperature and the use of high boiling solvents. Only inexpensive and readily available starting materials are required. The bis-lactim ethers were produced in high yields on a multigram scale. (c) 2006 Elsevier Ltd. All rights reserved.
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| 2. |
- Gullbo, Joachim, et al.
(författare)
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Antitumor efficacy and acute toxicity of the novel dipeptide melphalanyl-p-L-fluorophenylalanine ethyl ester (J1) in vivo.
- 2004
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Ingår i: Investigational new drugs. - 0167-6997. ; 22:4, s. 411-20
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Tidskriftsartikel (refereegranskat)abstract
- The novel alkylating dipeptide melphalanyl-p-L-fluorophenylalanine ethyl ester (J1) was evaluated for acute toxicity and antitumor activity in mice, with melphalan as a reference. To determine a safe and tolerable dose for efficacy studies the acute toxicity following intravenous injection in the tail vein was monitored using a 14-day schedule with up to four doses. The highest tested dose, 25 micromoles/kg, was considered close to this level, with minor effects on body weight gain but significant effects on hematological parameters. Melphalan and J1 appeared equitoxic with no statistically significant differences. Subsequently a mouse hollow fiber model was employed with subcutaneous implantation of fibers containing human tumor cells. Three different human tumor cell lines as well as two samples of primary human tumor cells (ovarian carcinoma and chronic lymphatic leukemia) were used as tumor models. At the dose level tested there was a marked and statistically significant decrease in both T-cell leukemia CCRF-CEM and small cell lung cancer NCI-H69 tumor cell growth and viability in response to J1 as compared with both placebo and melphalan treated groups. In primary ovarian carcinoma cells only J1 treatment resulted in significant tumor regression (net cell kill). In summary the results indicate that, despite an expected short half time in the blood circulation, the promising in vitro data from the previous studies of J1 seems translatable into the in vivo situation. At equal doses of alkylating units J1, compared to melphalan, was more active in the mouse hollow-fiber model, but showed similar general toxicity.
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| 3. |
- Jam, Fariba, 1967, et al.
(författare)
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Microwave assisted synthesis of spiro-2,5-diketopiperazines
- 2007
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Ingår i: Tetrahedron. - : Elsevier BV. - 0040-4020. ; 63, s. 9881-9889
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Tidskriftsartikel (refereegranskat)abstract
- A general and efficient method for the synthesis of spiro-2,5-diketopiperazines (spiro-DKPs) is described. Cyclization of Boc-protected dipeptides containing spiro-amino acids by microwave assisted heating in water furnished the corresponding spiro-DKPs. The spiro-amino acids were prepared by combining stereoselective alkylation reactions using the Schöllkopf methodology for amino acid construction with Grubbs ring-closing metathesis (RCM) methodology using ruthenium complexes. The RCM reactions and all subsequent transformations to the spiro-DKPs were run with microwave assisted heating, resulting in high yields and short reaction times for all steps.
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| 4. |
- Tullberg, Marcus, 1974, et al.
(författare)
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Efficient synthesis of 2,5-diketopiperazines using microwave assisted heating
- 2006
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Ingår i: Tetrahedron. - : Elsevier BV. - 0040-4020. ; 62:31, s. 7484-7491
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Tidskriftsartikel (refereegranskat)abstract
- In this study a general, efficient and environmentally benign solution phase synthesis of 2,5-diketopiperazines (DKPs) using microwave assisted heating in water is described. A series of 11 structurally different DKPs have been synthesized from dipeptide methyl esters. A range of common laboratory solvents have been tested as well as different reaction times and temperatures. Both classic thermal and microwave assisted heating have been investigated. Microwave assisted heating for 10 min using water as solvent proved, by far, to be the most efficient method of cyclization giving moderate to excellent yields (63-97%) of DKPs. In contrast to other published procedures, this method seems independent of the amino acid sequence. (c) 2006 Elsevier Ltd. All rights reserved.
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| 5. |
- Tullberg, Marcus, 1974, et al.
(författare)
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Microwave-assisted solid-phase synthesis of 2,5-diketopiperazines: solvent and resin dependence.
- 2006
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Ingår i: Journal of combinatorial chemistry. - : American Chemical Society (ACS). - 1520-4766 .- 1520-4774. ; 8:6, s. 915-22
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Tidskriftsartikel (refereegranskat)abstract
- Solid-phase synthesis of diketopiperazines (DKPs) was preformed using various combinations of resins (polystyrene, TentaGel, ArgoGel, and PEGA) and solvents (toluene, tert-butyl alcohol, water, and toluene/2-butanol (1:4, v/v). The DKPs were synthesized from solid-phase bound dipeptides via intramolecular aminolysis. Both thermal and microwave-assisted solid-phase synthesis of DKPs gave high yields of products independently of resin and organic solvent used; however, only the PEGA resin resulted in high yields of DKPs in water independent of heating method. The short reaction times, high yields, and the possibility to run reactions in water when an appropriate resin is used makes the microwave-assisted solid-phase synthesis the method of choice. The method should be suitable for solid-phase synthesis of diketopiperazine-based libraries.
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| 6. |
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| 7. |
- Tullberg, Marcus, 1974, et al.
(författare)
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Synthesis of functionalized, unsymmetrical 1,3,4,6-tetrasubstituted 2,5-diketopiperazines.
- 2007
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Ingår i: The Journal of organic chemistry. - : American Chemical Society (ACS). - 0022-3263 .- 1520-6904. ; 72:1, s. 195-9
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Tidskriftsartikel (refereegranskat)abstract
- A general and efficient method for the synthesis of unsymmetrical 1,3,4,6-tetrasubstituted 2,5-diketo- piperazines (DKPs) is described. Cyclization of N-amide alkylated dipeptide methyl esters, followed by alkylation, furnished the corresponding tetrasubstituted DKPs in good overall yields. The influence of steric hindrance in the alkylation reactions appeared to be of lesser importance as long as reactive alkylating agents were used. Furthermore, we have demonstrated the use of tetrasubstituted DKPs as a scaffold for further chemical manipulations to produce novel DKPs with desired properties.
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