(4R-(4R*,5S*,6S*,7R*,9R*,11E,13E,15S*,16R*))-16-Ethyl-4,6-dihydroxy-15-(hydroxymethyl)-5,9,13-trimethyl-2,10-dioxooxacyclohexadeca-11,13-diene-7-acetaldehyde, cyclic 5,20-hemiacetal

Base Information

• Chemical Name: (4R-(4R*,5S*,6S*,7R*,9R*,11E,13E,15S*,16R*))-16-Ethyl-4,6-dihydroxy-15-(hydroxymethyl)-5,9,13-trimethyl-2,10-dioxooxacyclohexadeca-11,13-diene-7-acetaldehyde, cyclic 5,20-hemiacetal
• CAS No.: 61219-81-6
• Molecular Formula: C₂₃H₃₆O₇
• Molecular Weight: 424.535
• Mol file: 61219-81-6.mol

Synonyms:(4R-(4R*,5S*,6S*,7R*,9R*,11E,13E,15S*,16R*))-16-Ethyl-4,6-dihydroxy-15-(hydroxymethyl)-5,9,13- trimethyl-2,10-dioxooxacyclohexadeca-11,13-diene-7- acetaldehyde, cyclic 5,20-hemiacetal

Chemical Property of (4R-(4R*,5S*,6S*,7R*,9R*,11E,13E,15S*,16R*))-16-Ethyl-4,6-dihydroxy-15-(hydroxymethyl)-5,9,13-trimethyl-2,10-dioxooxacyclohexadeca-11,13-diene-7-acetaldehyde, cyclic 5,20-hemiacetal

Chemical Property:

• Vapor Pressure: 3.45E-20mmHg at 25°C
• Boiling Point: 659.4°Cat760mmHg
• PKA: 13.12±0.70(Predicted)
• Flash Point: 222.8°C
• PSA: 113.29000
• Density: 1.094g/cm³
• LogP: 2.13870
• XLogP3: 2
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 2
• Exact Mass: 424.24610348
• Heavy Atom Count: 30
• Complexity: 656

Purity/Quality:

99% ^*data from raw suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CCC1C(C=C(C=CC(=O)C(CC2CC(OC2C(C(CC(=O)O1)O)C)O)C)C)CO
• Isomeric SMILES: CCC1C(/C=C(\C=C\C(=O)C(CC2CC(OC2C(C(CC(=O)O1)O)C)O)C)/C)CO
• General Description: (7E,9Z)-12-ethyl-2,16-dihydroxy-11-(hydroxymethyl)-5,9,17-trimethyl-3,3a,11,12,15,16,17,17a-octahydro-4H-furo[2,3-f]oxacyclohexadecine-6,14(2H,5H)-dione, also known as tylonolide hemiacetal, is a 16-membered ring macrolide antibiotic synthesized through a complex process involving the coupling of C(3)-C(9) and C(11)-C(17) fragments derived from chiral bicyclo[2.2.1]heptenol. The synthesis features key transformations such as benzoylation, olefin inversion, and allylic oxidation, employing reagents like benzyl chloride, boron trifluoride etherate, and lithium aluminum hydride to construct the macrolide core. (7E,9Z)-12-ethyl-2,16-dihydroxy-11-(hydroxymethyl)-5,9,17-trimethyl-3,3a,11,12,15,16,17,17a-octahydro-4H-furo[2,3-f]oxacyclohexadecine-6,14(2H,5H)-dione's structure includes a furo-oxacyclohexadecine scaffold with multiple functional groups, including hydroxyl and hydroxymethyl substituents, contributing to its biological activity.

Technology Process of (4R-(4R*,5S*,6S*,7R*,9R*,11E,13E,15S*,16R*))-16-Ethyl-4,6-dihydroxy-15-(hydroxymethyl)-5,9,13-trimethyl-2,10-dioxooxacyclohexadeca-11,13-diene-7-acetaldehyde, cyclic 5,20-hemiacetal

There total 58 articles about (4R-(4R*,5S*,6S*,7R*,9R*,11E,13E,15S*,16R*))-16-Ethyl-4,6-dihydroxy-15-(hydroxymethyl)-5,9,13-trimethyl-2,10-dioxooxacyclohexadeca-11,13-diene-7-acetaldehyde, cyclic 5,20-hemiacetal which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 100.0%

(7E,9E)-(3aR,5R,11R,12R,16R,17S,17aS)-12-Ethyl-16-hydroxy-2-methoxy-5,9,17-trimethyl-11-(tetrahydro-pyran-2-yloxymethyl)-3,3a,4,5,11,12,15,16,17,17a-decahydro-2H-1,13-dioxa-cyclopentacyclohexadecene-6,14-dione (61257-06-5) → Tylonolide Hemiacetal (61219-81-6)

Guidance literature:

With acetic acid; at 85 ℃; for 1h;

DOI:10.1021/ja00384a061

Reference yield:

(5R,6S)-5-(2-Benzyloxy-ethyl)-6-[(S)-2-(tert-butyl-diphenyl-silanyloxy)-1-methyl-ethyl]-tetrahydro-pyran-2-one (83061-04-5) → (+)-tylonolide hemiacetal (61219-81-6,108510-20-9,108510-21-0)

Guidance literature:

Multi-step reaction with 16 steps

1: LDA / tetrahydrofuran / -78 deg C -> -40 deg C

2: hydrogen / Pd-C / ethanol

3: CrO₃*2Py / CH₂Cl₂

4: TsOH

5: 95 percent / LiAlH₄ / diethyl ether / 0 °C

6: 95 percent / CrO₃*2Py / CH₂Cl₂ / 1 h / 0 °C

8: LiAlH₄ / tetrahydrofuran / 5 °C

9: DMAP, Py

11: 1.) CrO₃*2Py / 1.) 0 deg C, 2.) THF, -78 deg C, 10 min

12: sodium methoxide / methanol

13: 1 N NaOH / methanol / 2 h / 60 °C

14: triphenylphosphine / tetrahydrofuran

15: toluene / 24 h / Heating

16: 1.) MnO₂, 2.) aq. acetic acid / 1.) CH₂Cl₂, 3 h, 2.) tetrahydrofuran

With pyridine; dmap; manganese(IV) oxide; sodium hydroxide; lithium aluminium tetrahydride; hydrogen; sodium methylate; dipyridine chromium trioxide; toluene-4-sulfonic acid; acetic acid; triphenylphosphine; lithium diisopropyl amide; palladium on activated charcoal; In tetrahydrofuran; methanol; diethyl ether; ethanol; dichloromethane; toluene;

DOI:10.1021/ja00385a038

Reference yield:

(5R,6S)-5-(2-Benzyloxy-ethyl)-6-[(S)-2-(tert-butyl-diphenyl-silanyloxy)-1-methyl-ethyl]-3-methyl-tetrahydro-pyran-2-one → (+)-tylonolide hemiacetal (61219-81-6,108510-20-9,108510-21-0)

Guidance literature:

Multi-step reaction with 15 steps

1: hydrogen / Pd-C / ethanol

2: CrO₃*2Py / CH₂Cl₂

3: TsOH

4: 95 percent / LiAlH₄ / diethyl ether / 0 °C

5: 95 percent / CrO₃*2Py / CH₂Cl₂ / 1 h / 0 °C

7: LiAlH₄ / tetrahydrofuran / 5 °C

8: DMAP, Py

10: 1.) CrO₃*2Py / 1.) 0 deg C, 2.) THF, -78 deg C, 10 min

11: sodium methoxide / methanol

12: 1 N NaOH / methanol / 2 h / 60 °C

13: triphenylphosphine / tetrahydrofuran

14: toluene / 24 h / Heating

15: 1.) MnO₂, 2.) aq. acetic acid / 1.) CH₂Cl₂, 3 h, 2.) tetrahydrofuran

With pyridine; dmap; manganese(IV) oxide; sodium hydroxide; lithium aluminium tetrahydride; hydrogen; sodium methylate; dipyridine chromium trioxide; toluene-4-sulfonic acid; acetic acid; triphenylphosphine; palladium on activated charcoal; In tetrahydrofuran; methanol; diethyl ether; ethanol; dichloromethane; toluene;

DOI:10.1021/ja00385a038

upstream raw materials:

acetic anhydride

5-O-mycaminosyltylonolide N-oxide

15-[[(6-deoxy-2,6-di-O-methyl-β-D-allopyranosyl)-oxy]methyl]-6-[[3,6-dideoxy-4-O-(2,6-dideoxy-3-C-methyl-α-L-ribo-hexapyranosyl)-3-(dimethylamino)-β-D-glucopyranosyl]oxy]-16-ethyl-4-hydroxy-5,9,13-trimethyl-2,10-oxo-oxocyclo-hexadeca-11,13-diene-7...

demycarosyltylosin

Downstream raw materials:

(7E,9E)-(2S,3aR,5R,6S,11R,12R,16R,17S,17aS)-12-Ethyl-6,16-dihydroxy-2-methoxy-5,9,17-trimethyl-11-trityloxymethyl-2,3,3a,4,5,6,11,12,15,16,17,17a-dodecahydro-1,13-dioxa-cyclopentacyclohexadecen-14-one

(7E,9E)-(2S,3aR,5R,6R,11R,12R,16R,17S,17aS)-12-Ethyl-6,16-dihydroxy-2-methoxy-5,9,17-trimethyl-11-trityloxymethyl-2,3,3a,4,5,6,11,12,15,16,17,17a-dodecahydro-1,13-dioxa-cyclopentacyclohexadecen-14-one

(3R,4S)-4-[(2S,3R,5S)-3-((4E,6E)-(2R,3S,8R,9R)-3,9-Dihydroxy-2,6-dimethyl-8-trityloxymethyl-undeca-4,6-dienyl)-5-methoxy-tetrahydro-furan-2-yl]-3-hydroxy-pentanoic acid methyl ester

(3R,4S)-4-[(2S,3R,5S)-3-((4E,6E)-(2R,3S,8R,9R)-3,9-Dihydroxy-2,6-dimethyl-8-trityloxymethyl-undeca-4,6-dienyl)-5-methoxy-tetrahydro-furan-2-yl]-3-hydroxy-pentanoic acid

Refernces

Bicyclo<2.2.1>heptanes in Organic Synthesis. Total Synthesis of the 16-Membered Ring Macrolide Tylonolide Hemiacetal: Synthesis and Coupling of the C(3)-C(9) and C(11)-C(17) Fragments

10.1021/ja00385a038

The research involves two separate studies. The first study focuses on the total synthesis of the 16-membered ring macrolide antibiotic tylonolide hemiacetal. Key chemicals used in this research include chiral bicyclo[2.2.1]heptenol, which was elaborated into the C(3)-C(9) and C(11)-C(17) fragments through a series of complex organic reactions involving reagents such as benzyl chloride, boron trifluoride etherate, lithium aluminum hydride, and m-chloroperbenzoic acid. The synthesis also utilized various solvents like methylcyclohexane and tetrahydrofuran, and involved steps like benzoylation, olefin inversion, and allylic oxidation to ultimately achieve the coupling of the fragments and the formation of the 16-membered macrolide ring. The second study investigates the photochemical formation of tetracarbonyl(4,4’-dialkyl-2,2’-bipyridine)metal from hexacarbonylmetal using rapid-scan Fourier transform infrared spectroscopy. Chemicals such as W(CO)6, 4,4’-(n-C19H39)2-2,2’-bpy, and 2-phenylpyridine were used to observe the formation of monodentate intermediates in the reaction. The study provides direct infrared spectral evidence for the formation of these intermediates, highlighting the role of CO and the bipyridine ligands in the photochemical process.