|
|
| | (R)-N-Fmoc-2-(7'-octenyl) alanine Basic information |
| Product Name: | (R)-N-Fmoc-2-(7'-octenyl) alanine | | Synonyms: | (R)-N-Fmoc-2-(7'-octenyl) alanine;(2R)-2-[[(9H-Fluoren-9-ylmethoxy)carbonyl]amino]-2-methyl-9-decenoic acid;(R)-N-(9-Fluorenylmethylcarbamate)-2-(2'-octenyl)alanine;(R)-N-FMoc-2-(7'-octenyl) alanine, 97%Min;(R)-2-((((9H-Fluoren-9-yl)Methoxy)carbonyl)aMino)-2-Methyldec-9-enoic acid;FMoc-α-Me-D-Gly(Octenyl)-OH;(2R)-2-({[(9H-fluoren-9-yl)methoxy]carbonyl}amino)-2-methyldec-9-enoic acid;(R)-2-(Fmoc-amino)-2-methyldec-9-enoic acid | | CAS: | 945212-26-0 | | MF: | C26H31NO4 | | MW: | 421.53 | | EINECS: | | | Product Categories: | α-Methyl Amino Acids | | Mol File: | 945212-26-0.mol |  |
| | (R)-N-Fmoc-2-(7'-octenyl) alanine Chemical Properties |
| Boiling point | 588.3±45.0 °C(Predicted) | | density | 1.140 | | storage temp. | -20°C | | pka | 3.94±0.41(Predicted) | | form | liquid | | color | pale yellow | | Major Application | peptide synthesis | | InChIKey | MADFVGMQNXRFAF-AREMUKBSSA-N | | SMILES | C(O)(=O)[C@@](NC(OCC1C2=C(C=CC=C2)C2=C1C=CC=C2)=O)(C)CCCCCCC=C |
| Hazard Codes | N | | Risk Statements | 50 | | Safety Statements | 61 | | RIDADR | UN 3077 9 / PGIII | | WGK Germany | 3 | | TSCA | No | | HazardClass | 9 | | HS Code | 2922498590 | | Storage Class | 11 - Combustible Solids | | Hazard Classifications | Aquatic Acute 1 |
| | (R)-N-Fmoc-2-(7'-octenyl) alanine Usage And Synthesis |
| Uses | (2R)-2-[[(9H-Fluoren-9-ylmethoxy)carbonyl]amino]-2-methyl-9-decenoic Acid, is a stable antimicrobial peptide, that can be isolated from the venom of wild bee Lasioglossum laticeps. | | Uses | Olefinic alpha-methyl amino acid for peptide stapling. Upon incorporation of this amino acid into a peptide, along with another of the same or derivative with a different length of the olefinic side chain, the two can be ′stapled′ via a ring closing metathesis reaction with Grubb′s catalyst (product # 579726). The resulting stapled peptide macrocycle has been shown to stabilize the alpha-helical structure of peptides, which can lead to favorable biological characteristics such as increased proteolytic stability and cellular uptake. | | reaction suitability | reaction type: Fmoc solid-phase peptide synthesis | | Synthesis | 1. 1.55 kg (1.0 eq.) of 37-amino-2-methyl-dec-9-enoic acid hydrochloride (XIII) was suspended in 22 L of water and polished and filtered to remove traces of D-BPB hydrochloride.
2. Methyl tert-butyl ether was added and the aqueous product layer was extracted once with methyl tert-butyl ether.
3. The aqueous product layer was added again and 7 L of tetrahydrofuran was added.
4. 20% aqueous sodium carbonate (2.75 eq.) was added to the mixture followed by Fmoc-OSu (0.89 eq.).
5. The reaction was carried out at 20-25 °C, maintaining the pH at 8.5-9.0 by adding additional amounts of 20% sodium carbonate solution until the reaction was complete.
6. Adjust the pH of the mixture to 2.0-2.5 with concentrated hydrochloric acid.
7. The tetrahydrofuran is removed by distillation and methyl tert-butyl ether is added.
8. Separate the layers and wash the organic layer with water 3 times.
9. The organic layer is concentrated in vacuum and azeotropically distilled with methyl tert-butyl ether.
10. The crude oily substance is dissolved in methyl tert-butyl ether, cyclohexylamine (1.10 eq.) is slowly added, and the pH is adjusted to 8.5-9.0.
11. The slurry was stirred at 20-25 °C for 3 h. The solid product salt (XIV) was isolated by filtration.
12. The solids were rinsed twice with methyl tert-butyl ether and the wet cake was reloaded into a clean reactor.
13. The wet cake was recrystallized with tetrahydrofuran and methyl tert-butyl ether to improve purity.
14. The solid salt is suspended in methyl tert-butyl ether and water and the pH is adjusted to 2.0-2.5 with 25% sulfuric acid.
15. The organic product layer was washed with water until no cyclohexylamine remained.
16. The organic layer was concentrated and azeotropically distilled with hexane to a loose oil. 17.
17. The product (IIa) was crystallized from chloroform and hexane and purged dry with 1.0 cfm nitrogen at <0 °C. The product (IIa) was then purged dry at <0 °C with 1.0 cfm nitrogen.
Yield: 1.12 kg, 41.5% yield.
Recrystallization procedure:
18. Acetonitrile (23 mL/10 g of raw material ((R)-Ala-Ni-BPB(XI) in oil)) was added to the crude product and the mixture was heated to 70 °C and held for 30 min, then cooled to 20 °C. The mixture was purified with aqueous nitrogen.
19. The mixture was filtered and the solids were washed with acetonitrile (5 mL) and methyl tert-butyl ether (8.5 mL) to give a crystalline product. | | References | [1] Patent: US2014/128581, 2014, A1. Location in patent: Paragraph 0087; 0156; 0157 |
| | (R)-N-Fmoc-2-(7'-octenyl) alanine Preparation Products And Raw materials |
|