172923-77-2

Basic information

• Product Name: macrosphelide A
• Synonyms: macrosphelide A
• CAS NO: 172923-77-2
• Molecular Formula: C₁₆H₂₂O₈
• Mol File: 172923-77-2.mol

Chemical Properties

• Appearance: /
• CAS DataBase Reference: macrosphelide A(CAS DataBase Reference)
• NIST Chemistry Reference: macrosphelide A(172923-77-2)
• EPA Substance Registry System: macrosphelide A(172923-77-2)

Safety Data

• Hazardous Substances Data: 172923-77-2(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Macrosphelide A is used as an antibacterial agent for its ability to inhibit the growth of ascomycetes, basidomycetes, and other gram-positive bacteria. This property makes it a potential candidate for the development of new antibiotics to combat bacterial infections.
Used in Antifungal Applications:
In the field of antifungal research, macrosphelide A is utilized as an antifungal agent due to its effectiveness in inhibiting the growth of various fungi. This characteristic can be harnessed for the treatment of fungal infections and the development of antifungal medications.
Used in Cancer Research:
Macrosphelide A is also being explored for its potential use in cancer research, given its cytotoxic properties. It may be employed as a compound in the development of novel anticancer drugs, targeting cancer cells and potentially enhancing the effectiveness of existing cancer treatments.
Used in Drug Delivery Systems:
Similar to gallotannin, macrosphelide A can be incorporated into drug delivery systems to improve its bioavailability and therapeutic outcomes. By using various organic and metallic nanoparticles as carriers, the delivery, efficacy, and overall performance of macrosphelide A in treating bacterial and fungal infections can be enhanced.

Upstream product

• 554420-08-5 14-deoxymacrosphelide C 
• 503026-40-2 (E)-(4R,5S)-5-Hydroxy-4-(4-methoxy-benzyloxy)-hex-2-enoic acid 2-(toluene-4-sulfonyl)-ethyl ester 
• 503026-39-9 (E)-(4R,5S)-5-Formyloxy-4-(4-methoxy-benzyloxy)-hex-2-enoic acid 2-(toluene-4-sulfonyl)-ethyl ester 
• 294198-50-8 2,2,2-trichloroethyl (4R,5S)-4-benzyloxy-5-hydroxy-2(E)-hexenoate 
• 266323-53-9 (2S,6S,9E,11R,12S)-6,12-dimethyl-2-(2-furyl)-11-(methoxymethoxy)-14-(4-methoxyphenyl)-3,7,13-trioxa-9-tetradecene-4,8-dione 
• 266323-51-7 (2S,6S,9E,12S)-6,12-dimethyl-2-(2-furyl)-14-(4-methoxyphenyl)-3,7,13-trioxa-9-tetradecene-4,8,11-trione 
• 266323-52-8 (2S,6S,9E,11R,12S)-6,12-dimethyl-2-(2-furyl)-11-hydroxy-14-(4-methoxyphenyl)-3,7,13-trioxa-9-tetradecene-4,8-dione 
• 266323-46-0 (E)-(4R,5S)-5-Hydroxy-4-methoxymethoxy-hex-2-enoic acid (S)-2-((E)-(S)-4-carboxy-1-methyl-2-oxo-but-3-enyloxycarbonyl)-1-methyl-ethyl ester 
• 266323-57-3 (7E,13E)-(4S,9R,10S,15S,16S)-15-Hydroxy-9-methoxymethoxy-4,10,16-trimethyl-1,5,11-trioxa-cyclohexadeca-7,13-diene-2,6,12-trione 
• 266323-56-2 (7E,13E)-(4S,9R,10S,16S)-9-Methoxymethoxy-4,10,16-trimethyl-1,5,11-trioxa-cyclohexadeca-7,13-diene-2,6,12,15-tetraone 
• 266323-55-1 (E)-(4R,5S)-5-Hydroxy-4-methoxymethoxy-hex-2-enoic acid (S)-1-methyl-2-((E)-(S)-1-methyl-2,5-dioxo-pent-3-enyloxycarbonyl)-ethyl ester 
• 266323-54-0 (2S,6S,9E,11R,12S)-6-methyl-2-(2-furyl)-12-hydroxy-11-(methoxymethoxy)-3,7-dioxa-9-tridecene-4,8-dione 
• 266323-49-3 (2S,6S)-6-[(tert-butyldimethylsilyl)oxy]-2-(2-furyl)-3-oxa-4-heptanone 
• 266323-48-2 (2E,5S)-5-(4-methoxybenzyloxy)-4-oxo-2-hexenoic acid 

Downstream Products

• 172923-78-3 (5R,6S,12S,16S)-(3E,9E)-5-hydroxy-6,12,16-trimethyl-1,7,13-trioxacyclohexadeca-3,9-diene-2,8,11,14-tetraone 

Relevant articles and documents

Total synthesis of macrosphelide A by way of palladium-catalyzed carbonylative esterification

We achieved the total synthesis of macrosphelide A, as part of a combinatorial library of its analogues. The key intermediate, the seco-acid derivative, was prepared from the corresponding vinyl iodide using sequential carbonylative esterification.

Absolute stereochemistries and total synthesis of (+)/(-)-macrosphelides, potent, orally bioavailable inhibitors of cell-cell adhesion

In the current studies, we used the single-crystal X-ray analysis and Kakisawa-Kashman modification of the Mosher NMR method to determine the complete relative and absolute stereochemistries of the (+)-macrosphelides A (+)-1 and B (+)-2. The stereostructure of (+)-2 was determined by chemical comparison with artificial (+)-2 from (+)-1. We also report the convergent total synthesis of (+)-1 and (+)-3, as well as their antipodes, utilizing an asymmetric dihydroxylation for introduction of chirality and Yamaguchi macrocyclization to form the 16-membered trilactone macrolides.

General Stereodivergent Enantioselective Total Synthetic Approach toward Macrosphelides A-G and M

A straightforward enantioselective total synthesis algorithm for the preparation of 8 out of 13 macrosphelides within 9-11 steps starting from tert-butyl sorbate is presented. The use of a cyclic sulfate as both protecting and reactivity directing group is the key element within this algorithm. A high-pressure transesterification allows for the selective ring-enlargement of the 15-membered macrosphelides into the 16-membered counterparts. The absolute configurations of the natural products were unambiguously assigned both by the chemical synthesis and by X-ray structure analysis.

Enantioselective total synthesis of macrosphelides A and e

Enantioselective synthesis of 16-membered trilactone macrolides, macrosphelide A and E from (S)-lactic acid is described. Key features of the synthesis include the utility of a hitherto unexplored β-ketophosphonate derived from lactic acid and Yamaguchi lactonization leading to the title compounds.

Total Synthesis of Macrosphelides A, B, and E: First Application of Ring-Closing Metathesis for Macrosphelide Synthesis

A new synthetic route for macrosphelides A, B, and E based on ring-closing metathesis (RCM) was established. The substrates for RCM could be synthesized starting from commercially available chiral materials, methyl (S)-lactate and methyl (S)- or (R)-3-hydroxybutyrate, in good overall yields. In the investigation of the key RCM step, it was found that the steric factor around the reaction site significantly affected the reaction rate of macrocyclization. A detailed account regarding this synthetic study is described herein.

New strategy for the total synthesis of macrosphelides A and B based on ring-closing metathesis

(Matrix presented) A new total synthesis of macrosphelides A and B using ring-closing metathesis (RCM) as a macrocyclization step is described. The substrate of the RCM could be synthesized from readily available chiral materials, methyl (S)-(+)-3-hydroxybutyrate and methyl (S)-(-)-lactate, with a high efficiency. The RCM proceeded in the presence of Grubbs' Ru-complex, providing a new effective synthetic route to these natural products.

A Combinatorial Synthesis of a Macrosphelide Library Utilizing a Palladium-Catalyzed Carbonylation on a Polymer Support

Supported total synthesis: The combinatorial synthesis of a 122-membered macrosphelide library including macrosphelides A, C, E, and F (see picture) has been achieved based on a unique strategy for a three-component coupling utilizing a palladium-catalyzed chemoselective carbonylation and an unprecedented macrolactonization on a polymer support.

Synthesis of various macrosphelides by oxidative derivatization of the macrosphelide core

The macrosphelide core (4), simple 16-membered trilactone, was subjected to several oxidative conditions to produce various natural macrosphelide analogues, including macrosphelides A and C. This approach provided a new access to diverse macrosphelides for a study on their structure-activity relationships.

The total synthesis of macrosphelides A and E from carbohydrate precursors

The total synthesis of macrolide antibiotics, macrosphelide A and E has been achieved starting from carbohydrate precursors.

Furan ring oxidation strategy for the synthesis of macrosphelides A and B

By using the convenient protocol for conversion of 2-substituted furans into 4-oxo-2-alkenoic acids ((i) NBS, (ii) NaClO2), macrosphelide B (2) was synthesized from furyl alcohol 5 (> 98% ee) and acid 6 (99% ee). The protocol was first applied to the PMB ether of 5 to afford acid 13b. On the other hand, DCC condensation of acid 6 with 5 gave 16 after deprotection of the TBS group. Condensation was again carried out between 13b and 16 to furnish the key ketone 17, which upon reduction with Zn(BH4)2 afforded anti alcohol 18 stereoselectively (15:1). After protection/deprotection steps, the furan 18 was converted to seco acid 3 by using the furan oxidation protocol mentioned above, and lactonization of 3 with Cl3C6H2COCl, Et3N, and DMAP afforded 22 (MOM ether of 2), which upon deprotection with TFA produced 2. Transformation of 22 to macrosphelide A (1) was then investigated. Although the chelation-controlled reduction of 22 should afford the desired anti alcohol 24, Zn(BH4)2 at 4 in MeOH at -15 °C produced the syn isomer 23 with > 10:1 diastereoselectivity. Mitsunobu inversion of the resulting C(14)-hydroxyl group and deprotection of the MOM group with TFA afforded 1. Similarly, reduction of 2 with NaBH4 afforded the C(14)-epimer of 1 stereoselectively. The observed stereoselectivity in the reductions of 22 and 2 could be explained on the basis of computer-assisted calculation, which showed presence of the low-energy conformers responsible for the stereoselective reduction. In addition, conversion of 2 to 1 was established, for the first time.