943515-58-0

Basic information

• Product Name: 3,4-O-(DiethylMethylidene) ShikiMic Acid Ethyl Ester
• Synonyms: 3,4-O-(DiethylMethylidene) ShikiMic Acid Ethyl Ester
• CAS NO: 943515-58-0
• Molecular Formula: C₁₄H₂₂O₅
• Molecular Weight: 270.32148
• Product Categories: Chiral Reagents, Pharmaceuticals, Intermediates & Fine Chemicals
• Mol File: 943515-58-0.mol

Chemical Properties

• Boiling Point: 384.1±42.0 °C(Predicted)
• Appearance: /
• Density: 1.132±0.06 g/cm3(Predicted)
• Storage Temp.: Hygroscopic, -20°C Freezer, Under inert atmosphere
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 13.40±0.60(Predicted)
• CAS DataBase Reference: 3,4-O-(DiethylMethylidene) ShikiMic Acid Ethyl Ester(CAS DataBase Reference)
• NIST Chemistry Reference: 3,4-O-(DiethylMethylidene) ShikiMic Acid Ethyl Ester(943515-58-0)
• EPA Substance Registry System: 3,4-O-(DiethylMethylidene) ShikiMic Acid Ethyl Ester(943515-58-0)

Safety Data

• Hazardous Substances Data: 943515-58-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
3,4-O-(Diethylmethylidene) Shikimic Acid Ethyl Ester is used as a reactant for the preparation of oseltamivir analogs, which are neuraminidase inhibitors. These analogs are specifically designed to combat avian influenza virus, providing a crucial defense against this infectious disease. 3,4-O-(DiethylMethylidene) ShikiMic Acid Ethyl Ester's role in the synthesis of these antiviral agents highlights its importance in the development of effective treatments for viral infections.

Upstream product

• 138-59-0 shikimic acid 
• 101769-63-5 (3R,4S,5R)-3,4,5-trihydroxycyclohex-1-ene-1-carboxylic acid ethyl ester 
• 96-22-0 pentan-3-one 
• 1346667-84-2 (3aR,7S,7aR)-ethyl 2,2-diethyl-7-(trifluoromethylsulfonyloxy)-3a,6,7,7a-tetrahydrobenzo[d][1,3]dioxole-5-carboxylate 
• 1201685-66-6 (3aR,4S,7aR)-6-(ethoxycarbonyl)-2,2-diethyl-3a,4,5,7a-tetrahydrobenzo[d][1,3]dioxol-4-yl methanesulfonate 
• 1201685-54-2 ethyl (3aR,7S,7aS)-2,2-diethyl-7-hydroxy-3a,6,7,7a-tetrahydrobenzo[d][1,3]dioxole-5-carboxylate 
• 1201685-50-8 ethyl (S)-4-((4S,5R)-2,2-diethyl-5-vinyl-1,3-dioxolan-4-yl)-4-hydroxy-2-methylenebutanoate 
• 1218790-10-3 (4R,5R)-2,2-diethyl-5-vinyl-1,3-dioxolane-4-carbaldehyde 
• 1201685-62-2 methyl 5-deoxy-5-iodo-2,3-O-isopentylidene-β-D-ribofuranose 
• 1201685-58-6 methyl 2,3-O-isopentylidene-β-D-ribofuranose 
• 36749-09-4 3,3-diethoxypentane 
• 1393086-01-5 C₂₅H₃₇O₉P 

Downstream Products

• 204255-06-1 oseltamivir 
• 204255-11-8 oseltamivir phosphate 
• 204254-92-2 ethyl (3R,4R,5R)-3-(1-ethyl-propoxy)-4-hydroxy-5-methanesulfonyloxycyclohex-1-ene-1-carboxylate 
• 367252-68-4 (3R,4R,5S)-ethyl 4-acetamido-5-((tert-butoxycarbonyl)amino)-3-(pentan-3-yloxy)cyclohex-1-enecarboxylate 
• 1393086-08-2 C₂₁H₃₁NO₄ 
• 1393086-10-6 C₁₆H₂₇NO₅ 
• 1393086-07-1 C₁₆H₂₇NO₅ 
• 1393086-06-0 C₂₁H₃₁NO₆S 
• 1393086-09-3 C₂₁H₃₁NO₆S 
• 1393086-05-9 C₂₁H₂₉NO₄ 
• 1393086-03-7 C₂₁H₂₉NO₆S 
• 1234287-06-9 ethyl (3R,4S,5S)-4-(1-ethyl-propoxy)-3-hydroxy-5-tert-butoxycarbonylaminocyclohex-1-ene-1-carboxylate 
• 1234287-00-3 ethyl (3R,4S,5S)-3-(1-ethylpropoxy)-4-hydroxy-5-amino-cyclohex-1-ene-1-carboxylate 
• 367252-67-3 (3R,4R,5S)-4-azido-5-tert-butoxycarbonylamino-3-(1-ethylpropoxy)cyclohex-1-enecarboxylic acid ethyl ester 

Relevant articles and documents

Crystallization method of intermediate 5 of high-purity oseltamivir phosphate

5 (Pentane 5 -yloxy) -3 - oxo -7 - bicyclo [-] hep 4.1.0-3 -3 - carboxylate ethyl carboxylate is concentrated to precipitate crystals, and then crystals are directly put into a mixed solvent composed of an alkane solvent and an alcohol solvent. Through the crystallization method, the purity of the intermediate 5 can reach above 99.7%, and the requirement for preparing oseltamivir phosphate is completely met.

Synthesis of some carbahexopyranoses using Mn/CrCl3 mediated domino reactions and ring closing metathesis

An efficient and common method for the synthesis of 5a-carba-α-D-mannopyranose 5, 5a-carba-β-D-mannopyranose 6, (+) methyl shikimate 9, (+) methyl-5-epi-shikimate 10, validamine analogue 15 and valiolamine analogue 16 from D-mannose, formal synthesis of T

New Method for the Rapid Extraction of Natural Products: Efficient Isolation of Shikimic Acid from Star Anise

A new, practical, rapid, and high-yielding process for the pressurized hot water extraction (PHWE) of multigram quantities of shikimic acid from star anise (Illicium verum) using an unmodified household espresso machine has been developed. This operationa

A concise and practical synthesis of oseltamivir phosphate(Tamiflu) from d-mannose

A short and practical synthesis of oseltamivir phosphate was accomplished in 11 steps from inexpensive and abundant starting material, d-mannose. This synthetic route featured an intramolecular Horner-Wadsworth-Emmons reaction as the key step to furnish the cyclohexene ring product. The hydroxyl group was converted stereo specifically into an amino group by oxidation to the ketone and reductive amination whereas the second amino group was introduced by azide substitution of a hydroxyl group. This synthesis provided an economical and practical alternative for the synthesis of Tamiflu.

A new efficient synthesis of oseltamivir phosphate (Tamiflu) from (-)-shikimic acid

New synthesis of oseltamivir phosphate was accomplished in 9 steps with a 27% overall yield from a readily available (-)-shikimic acid. Selective ring opening reaction of ketal and azide Mitsunobu reaction for facile replacement of a hydroxyl group by the N3 group at the C-3 position of (3R,4R,5R)-ethyl 4-hydroxy-5-(methoxymethoxy)-3-(pentan-3-yloxy)cyclohex-1-enecarboxylate 4 and at the C-4 position of (3R,4S,5R)-ethyl 4-acetamido-5-hydroxy-3-(pentan-3-yloxy) cyclohex-1-enecarboxylate 7 successfully served as the key steps.

Synthesis and in vitro study of novel neuraminidase inhibitors against avian influenza virus

Evidences of oseltamivir resistant influenza patients raised the need of novel neuraminidase inhibitors. In this study, five oseltamivir analogs PMC-31-PMC-36, synthesised according to the outcomes of a rational design analysis aimed to investigate the effects of substitution at the 5-amino and 4-amido groups of oseltamivir on its antiviral activity, were screened for their inhibition against neuraminidase N1 and N3. The enzymes used as models were from the avian influenza A H7N1 and H7N3 viruses. The neuraminidase inhibition assay was carried out by using recombinant species obtained from a baculovirus expression system and the fluorogenic substrate MUNANA. The assay was validated by using oseltamivir carboxylate as a reference inhibitor. Among the tested compounds, PMC-36 showed the highest inhibition on N1 with an IC50 of 14.6 ± 3.0 nM (oseltamivir 25 ± 4 nM), while PMC-35 showed a significant inhibitory effect on N3 with an IC50 of 0.1 ± 0.03 nM (oseltamivir 0.2 ± 0.02 nM). The analysis of the inhibitory properties of this panel of compounds allowed a preliminary assessment of a structure-activity relationship for the modification of the 4-amido and 5-amino groups of oseltamivir carboxylate. The substitution of the acetamido group in the oseltamivir structure with a 2-butenylamido moiety reduced the observed activity, while the introduction of a propenylamido group was well tolerated. Substitution of the free 5-amino group of oseltamivir carboxylate with an azide, decreased the activity against both N1 and N3. When these structural changes were both introduced, a dramatic reduction of activity was observed for both N1 and N3. The alkylation of the free 5-amino group in oseltamivir carboxylate introducing an isopropyl group seemed to increase the inhibitory effect for both N1 and N3 neuraminidases, displaying a more pronounced effect against N1.

Expeditious access to (-)-shikimic acid derivatives for Tamiflu synthesis

A three-step, one-pot process has been developed for the synthesis of 5-epi-shikimic acid derivative 5 using inexpensive and abundant D-ribose as the starting material. Based on this pivotal intermediate, the syntheses of two key shikimic acid derivatives

EPOXIDE INTERMEDIATE IN THE TAMIFLU SYNTHESIS

The present invention relates to technology for preparing derivatives of unsaturated, cyclic, organic acids and salts, thereof. Shikimic acid is an example of such an acid. More particularly, the present invention relates to preparing derivatives of these acids or salts thereof that are esterified, ketalized, functionalized with a leaving group, and/or provided with epoxide functionality. Preferred aspects may be used in the synthesis of Oseltamivir Phosphate starting from shikimic acid.

Industrial synthesis of the key precursor in the synthesis of the anti-influenza drug oseltamivir phosphate (Ro 64-0796/002, GS-4104-02): Ethyl (3R,4S,5S)-4,5-epoxy-3-(1-ethyl-propoxy)-cyclohex-1 -ene-1 -carboxylate

Starting from (-)-quinic acid, the title compound was synthesized in seven chemical steps and an overall yield of 35-38%. The route of the improved Gilead synthesis was not changed. However, significant improvements in each step led to a doubled overall yield, a 30% reduction in the number of unit operations, and an excellent quality (≥99%) of the resulting epoxide. A highly regioselective method for the dehydration of a quinic acid to a shikimic acid derivative and for the reduction of a cyclic ketal was found. Alternatively, the title compound was synthesized in six chemical steps and 63-65% yield from commercially available (-)-shikimic acid. Compared to the optimized quinic acid route, the production time was reduced by about 50%. The quality of epoxide produced from either natural product was equivalent. Therefore (-)-shikimic acid is the preferred raw material. The absolute configuration of the epoxide was determined by X-ray single crystal structure analysis and it was demonstrated that the epoxide was stereo-isomerically pure.