ACRL toxins synthesis

Another highly versatile building block derived from diacetone-glucose 54 is the 1,2-acetonide of 3-C-methyl-a-D-allose in its furanoid form 57, which has been utilized as the key compound in a convergent total synthesis of ACRL Toxin I (63). Its elaboration from 54 starts with a pyridinium dichromate / acetic anhydride oxidation (64), is followed by carbonyl olefination of the respective 3-ulose with methyl (triphenyl)phosphonium bromide and hydrogenation (— 55 56), and is completed by acid cleavage of the 5,6-isopropylidene group. This four-step process 54 -> 57, upon optimization of reaction conditions and workup procedure, allows an overall yield of 58 % (63), as compared to the 22 % obtained previously (65). 

The utilization of the furanoid 3-C-methyl-D-allose building blocks 57 and 60 for a convergent total synthesis of ACRL Toxin I in the form of its stable 3-0-methyl ether (63) involved their conversion into enantiomerically uniform connective segments. The key feature of the retrosynthesis was the expectation... 

In the coming section, we will detail how Lichtenhaler put such retro-synthetic thinking into practice in his synthesis of the (—)-ACRL toxin I. 

Scheme 14.3 Lightenhaler s route to sub-target 8 in his (—)-ACRL toxin I synthesis.

After purification, the dimethyl 1,3-dioxinone unit of 2 was hydrolysed with mild base to furnish the P-keto acid. Acidification then brought about lactonisation to the enolised p-keto lactone 1. To facilitate work-up and isolation, the latter was converted to the vinylogous ester 24 with potassium carbonate and dimethylsulfate in acetone. Mild acid hydrolysis of 24 with 0.1 N H2S04 in EtOAc eventually furnished (-)-ACRL toxin 1 in good yield after six days, completing this very elegant and beautifully crafted synthesis. 

Lichtenhaler s synthesis of the (—)-ACRL toxin I shows good levels of stereocontrol except for the installation of one stereocentre, the C(5)-hydroxyl. Its longest linear sequence of only 20 steps, for installing six asymmetric centres and two stereodefined double bonds, corresponds to... 

Most Lewis acids such as zinc bromid in methanol, dichtoroethylalane in di-chloromethane, trifluoroborane etherate and ethane-1,2-dithiol in methanol,372 or iron(lll) chloride373 will also cleave trity ethers. Scheme 4.202 illustrates the use of zinc bromide in dichloromethane374 to remove a trityl ether in the presence of two a Hylic TBS ethers during a synthesis of ACRL toxin 111b.375... 

This review deals with recent advances in the synthesis of polypropionate structures. It focuses on the total synthesis of natural products (citreoviral, ACRL toxin IECB) as well as on new synthetic methodology (chiral methyl branching, base induced 1,3-H-shift and chiral methyl groups). 

ACRL toxins form a family of metabolites of the microorganism altemaria citri rough lemon which is reponsible for the brown spot disease of citrus fruits. All these toxins are polyene pyrone polyketides in different oxidation levels. When we started the project only one synthesis of an ACRL toxin was known, namely that one of ACRL toxin I by Lichtenthaler et al. (16). Later two additional syntheses of 128 were reported (17). Our retrosynthetic disconnection of 128 is shown in Scheme 21. It results in the formation of three fragments 129-131. The first one contains the trisubsti-tuted olefin unit which is accessible by the above-mentioned base induced 1,3-H-... 

Scheme 4. (a) Chiral auxiliaries in the form of a-oxygenated substrates to accomplish 1,2-anf/ aldol stereoselectivity in Paterson s total synthesis of ACRL Toxin IIIB (42) and (b) methods to remove the directing group. (1994) ... 

Lichtenthaler, F.W., J. Dinges, and F. Yoshimasa ACRL Toxin I Convergent Total Synthesis of its 3-Methyl Enol Ether from D-Glucose. Angew. Chem. Int. Ed. Engl., 30, 1339 (1991). 

Paterson I. Polyketide synthesis using the boron-mediated, aniialdol reactions of lactate-derived ketones total synthesis of (-)-ACRL Toxin IIIB. Synthesis 1998 639-650. 

---