Total synthesis and biological evaluation of apicularen A and synthetic analogs

Bhattacharjee, Ashoke; Seguil, Olga R.; Brabander, Jef K. De

doi:10.1016/s0040-4039(00)02245-0

Cited by 65 publications

(34 citation statements)

References 13 publications

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“…Again, the acyl part of the enamide can be modified, but without the enamide there is no activity. [10] A study by Nicolaou et al concurs closely with the observations mentioned above ( Figure 5); [11b] variations in the acyl part of the enamide, for example, are tolerated provided that the acyl part is neither too short nor too long. Minor modifications in the macrolactone, such as acetylation of the 11-OH function, cause only a small loss of activity.…”

supporting

confidence: 70%

“…Thus, the enamide could be fashioned from an α,β-unsaturated carboxylic acid by Curtius rearrangement, followed by trapping of the intermediate vinyl isocyanate with an organometallic nucleophile. [10] This approach hinges upon the availability of a suitable nucleophile. Another method is based on a cross-coupling reaction between an amide and a vinyl iodide.…”

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confidence: 99%

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Synthesis and Biological Evaluation of Apicularen A Analogues

2005

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Reactions between amide anions and propanal derivatives containing benzolactone components at their 3‐positions produced hemiaminals, which were dehydrated via the corresponding acetates to provide the apicularen A analogues 21, 29, 34, 38, and 41. Of these, 21 and 29 contain the intact enamide side chain of apicularen A but have modifications in the macrolactone core. On the other hand, compounds 34, 38, and 41 are characterized by the natural core structure but are modified in the enamide part. Biological studies showed that 21 and 29 are quite active but that the other three analogues show only minor activities. The 11‐deoxy analogue 21 turned out to be the most active compound against a mdr cell line. It can be concluded that the macrolactone part of apicularen A will tolerate modifications to some degree, whereas the enamide part is rather sensitive towards structural modifications. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

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confidence: 70%

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confidence: 99%

Synthesis and Biological Evaluation of Apicularen A Analogues

2005

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“…R f = 0.78 (petroleum ether/diethyl ether, 1:1); [a] 15 (266 mg, 0.80 mmol), and 3 n NaOH (0.89 mL). The mixture was heated to 40 8C for 4 h, cooled to room temperature, and diluted with Et 2 O (20 mL) and brine (20 mL (Si(CH 3 ) 2 ), À4.4 (Si(CH 3 ) 2 ), 14.1 (CH 3 ), 18.0 (SiC), 25.3 (C-10), 25.8 (C (CH 3 ) 3 ), 32.8 (C-9), 35.6 (C-4), 36.1 (C-1), 36.4 (C-5), 37.7 (C-7), 52.0 (CO 2 CH 3 ), 55.1 (PMB CH 3 ), 55.6 (MOM CH 3 ) 55.7 (PhÀOCH 3 ), 69.4 (C-8), 70.2 (C-11), 72.3 (PMB CH 2 ), 78.3 (C-6), 95.6 (MOM CH 2 ), 108.6 (C-3'), 113.6 (PMB C-3,5), 121.5 (C-5'), 123.3 (C-1'), 129.1 (PMB C-2,6), 129.1 (C-2), 130.3 (C-4'), 130.6 (PMB C-1), 130.7 (C-3), 139.2 (C-6'), 156.3 (C-2'), 159.0 (PMB C-4), 168.5 ppm (CO 2 CH 3 ); IR (film): ñ = 1038, 1071, 1109, 1249, 1470, 1513, 1734, 2855, 2931, 2952 cm À1 ; MS (EI): m/z (%): 293 (2), 192 (5), 181 (10), 178 (10), 176 (10), 170 (17), 168 (12), 166 (16), 150 (16), 141 (17), 137 (47), 121 (100), 97 (14), 77 (8) (8 mL), and H 2 O (8 mL) was treated with LiOH·H 2 O (271 mg, 6.46 mmol) and stirred at 70 8C for 3 days. After being allowed to cool to room temperature, the reaction mixture was diluted with Et 2 O (20 mL) and water (50 mL).…”

Section: Ethyl 6-[(4-methoxybenzyl)oxy]-3-oxohexanoate (5)mentioning

confidence: 99%

“…antitumor agents · lactonization · metathesis · salicylihalamide · total synthesis theses for the salicylihalamides [11] and apicularen A [12] have been described. In addition, formal total syntheses [13,14] and synthetic studies have been published.…”

Section: Introductionmentioning

confidence: 99%

Total Synthesis of Salicylihalamides A and B

Herb

Bayer

Maier

2004

Chemistry A European J

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The paper illustrates two efficient routes to macrolactone 19 containing a 3-(para-methoxybenzyloxy)propyl side chain at C-15. The chiral center at C-15 was introduced by a Noyori reduction of keto ester 5. The intermediate common to both routes, aldehyde 8, was prepared from keto ester 5. The subsequent chain extension utilized Evans aldol reactions. The first route leads to the alkene 14, which was used, after hydroboration, for a Suzuki cross-coupling reaction with vinyl iodide 15. The derived seco acid 18 was converted into the macrolactone 19 by a Mitsunobu lactonization by using immobilized triphenylphosphine. Alternatively, an aldol reaction of 8 with the 4-pentenoyl derivative 20 was used to prepare alkene 26. This building block led to ester 28, which could also be converted into macrolactone 19 by the classical ring-closing metathesis. After conversion of the C-15 side chain to the corresponding aldehyde, the enamide was introduced through hemiaminal formation and formal elimination of water. Separation of the double-bond isomers and removal of the silyl protecting groups provided salicylihalamides A (E)-1 and B (Z)-1.

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“…An interesting case at hand is a class of macrolides that embrace the oximidines, 1 the salicylihalamides 2-5 and the apicularens. [6][7][8] Related compounds include the lobatamides 9 and CJ-12,950 ( Figure 1). 10 Although these compounds originate from different sources, they nevertheless share common structural features.…”

mentioning

confidence: 99%