Synthetic studies on β-lactam antibiotics. VII. Mild removal of the benzyl ester protecting group with aluminum trichloride

Tsuji, Teruji; Kataoka, Takahiro; Yoshioka, M.; Sendo, Yuji; Nishitani, Yasuhiro; Hirai, Shoichi; Maeda, Takashi; Nagata, Wataru

doi:10.1016/s0040-4039(01)86418-2

Cited by 95 publications

(16 citation statements)

References 7 publications

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“…Deprotection of the tert-butyl ester is achieved using relatively mild acidic conditions. Lewis acid promoted hy-drolysis of cephalosporin esters is a procedure already reported for benzyl, 5 diphenylmethyl, 6 and 4methoxybenzyl 7 esters using aluminum trichloride. 8 The use of tin tetrachloride 8 and titanium tetrachloride 5,8 has also been advocated.…”

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confidence: 99%

Synthesis of the β-Lactamase Indicators Cefesone and Nitrocefin

Barendse¹,

Klein²,

Verweij³

et al. 1998

Synthesis

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The synthesis of the b-lactamase indicators Cefesone [(6R,7R)-3-(2,4-dinitrostyryl)-7-(phenylacetamido)ceph-3-em-4-carboxylic acid] and Nitrocefin [(6R,7R)-3-(2,4-dinitrostyryl)-7-(2thienylacetamido)ceph-3-em-4-carboxylic acid] from tert-butyl (1S,6R,7R)-3-bromomethyl-1-oxo-7-(phenylacetamido)ceph-3-em-4carboxylate is reported. Phosphonylation of the latter compound with triphenylphosphine gave the corresponding phosphonium derivative in 93% yield. Reduction followed by Wittig coupling with 2,4-dinitrobenzaldehyde gave a 1:12 mixture of E-and Z-isomers in 83% yield. The tert-butyl protecting group was removed with titanium tetrachloride to give Cefesone as the pure crystalline E-isomer in 63% yield. De-acylation was achieved by enzymatic hydrolysis in 77% yield. Finally the 2-thienylacetyl side chain was introduced to give crystalline Nitrocefin in 67% yield. Downloaded by: University of Pittsburgh. Copyrighted material. 1665 (CO, amide), 1525 cm -1 (NO 2 ). MS (DCI): m/z = 584.2 (MNH 4 + ). 1 H NMR (CDCl 3 ; 360 MHz): d = 1.53 (s, 9H, tert-butyl), 2.75 (d, 1H, J = 18.2 Hz, H 2 ), 3.25 (d, 1H, J = 18.2 Hz, H 2 ), 3.63 (ABq, 2H, J = 15.9 Hz, ArCH 2 ), 4.91 (d, 1H, J = 4.9 Hz, H 6 ), 5.84 (dd, 1H, J 6.7 = 4.9 Hz, J 7,NH = 9.1 Hz, H 7 ), 6.02 (d, 1H, J = 9.1 Hz, NH), 6.84 (ABq, 2H, J = 11.9 Hz, CH=CH), 7.3 (m, 5H, ArH), 7.57 (d, 1H, J = 8.6 Hz, ArH), 8.88 (d, 1H, J = 2.3 Hz, ArH).(6R,7R)-3-(2,4-Dinitrostyryl)-7-(phenylacetamido)ceph-3-em-4carboxylic Acid, E-Isomer (4): A stirred solution of 3 (67.41 g, purity 8% E-isomer, 81% Z-isomer, 105.9 mmol) in CH 2 Cl 2 (1685 mL) was cooled to -25 °C. TiCl 4 (53 mL, 482 mmol) was added in 10 min and the temperature was brought to 0°C. After 1.75 h, chilled 2 M HCl (1685 mL) was added at such a rate that the temperature remained under 10 °C. The organic phase was separated and extracted with 2 M HCI (2 ´1685 mL), H 2 O (1685 mL) and brine (1685 mL). The organic phase was concentrated under reduced pressure to give an orange foam. Crude 4 thus obtained was crystallized by dissolving in acetone (1350 mL) at 65 °C and adding H 2 O (675 mL). Crystallization was allowed to proceed for 16 h at 0°C and the crystals were collected by filtration. Recrystallization of the product was performed by dissolving the material in acetone/ HOAc (2:1) at 53 °C, removing the solvent (1700 mL) by evaporation under reduced pressure, and stirring for 16 h at 20 °C. Crystals were collected by filtration, washed with HOAc (300 mL) and Et 2 O (250 mL), and dried under vacuum at 45 °C to give 34.33 g (purity 99% E-isomer, 66.6 mmol; 63%) of 4 as yellow crystals. IR (KBr): n = 3300 (NH), 1780 (CO, b-lactam), 1715 (CO, amide), 1625 (CO, carboxylic acid), 1525 cm -1 (NO 2 ). MS (DCI): m/z = 528.0 (MNH 4 + ). 1 H NMR (CDCl 3 /DMSO-d 6, 1:2; 360 MHz): d = 3.50/3.58 (ABq, 2H, J = 14.1 Hz, ArCH 2 ), 3.62/3.77 (ABq, 2H, J = 17.5 Hz, H 2 ), 5.05 (d, 1H, J = 4.9 Hz, H 6 ), 5.72 (dd, 1H, J 6,7 = 4.9 Hz, J 7,NH = 8.3 Hz, H 7 ), 7.3 (m, 6H, ArH + CH=C), 7.63 (d, 1H, J = 16.1 Hz, C=CH), 7.82 (d, 1H, J = 8.8 Hz, ArH),...

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confidence: 99%

Synthesis of the β-Lactamase Indicators Cefesone and Nitrocefin

Barendse¹,

Klein²,

Verweij³

et al. 1998

Synthesis

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“…Further experimentation was attempted by employing standard Lewis acids including SiO 2 , CuI, and LiCl (entries 7–9) without success. AlCl 3 affected conversion of 3 to 4 , but with significant decomposition. Thermolytic degradation of the N ‐Boc group, in addition to discrete treatment of 3 with trifluoroethanol, were also unsuccessful.…”

Section: Resultsmentioning

confidence: 94%

Deprotection of N‐tert‐Butoxycarbonyl (Boc) Protected Functionalized Heteroarenes via Addition–Elimination with 3‐Methoxypropylamine

Gulledge

Carrick

2020

Eur J Org Chem

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Continued pursuit of functionalized soft‐N‐donor complexant scaffolds with favorable solubility and kinetics profiles applicable for the separation of the trivalent minor actinides from the lanthanides has attracted significant interest over the last three decades. Recent work from this laboratory resulted in the production of various N‐Boc protected [1,2,4]triazinyl‐pyridin‐2‐yl indole Lewis basic procomplexants which necessitated the removal of the indole N‐Boc protecting group prior to evaluation of complexant efficacy in separations assays. Traditional deprotection strategies involving trifluoroacetic and other protic and Lewis acids proved unsuccessful in removal of the recalcitrant indole‐N‐Boc protecting group necessitating the development of a new strategy for deprotection of this complexant class. A serendipitous result facilitated utilization of 3‐methoxypropylamine as a mild deprotecting agent for various N‐Boc protected heteroarenes via a proposed addition–elimination mechanism. Method development, application to various heteroarenes including indoles, 1,2‐indazoles, 1,2‐pyrazoles, and related derivatives, a ten‐fold scale‐up reaction, and experimental evaluation of a preliminary mechanistic hypothesis are reported herein.

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“…Condensation of 7 and 8 proceeded smoothly to give amide 22 18. Unmasking of the methyl‐protected phenolic hydroxy and Boc‐protected amino groups of 22 were effected in one pot by treating 22 with BBr 3 /CH 2 Cl 2 in the presence of anisole to afford 6 (amicoumacin C, isolated as its hydrochloride salt by treatment of 6 with HCl/MeOH) 19. The hydrochloride salt of 6 was treated with methanolic ammonia to give 4 (amicoumacin A), which was then mixed with 2,3‐butanedione under various sets of acidic conditions.…”

Section: Methodsmentioning

confidence: 99%

Total Synthesis of Bacilosarcins A and B

Enomoto

Kuwahara

2009

Angew Chem Int Ed

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I want to ride my bicycle: The thermodynamic stability of nitrogen‐containing heterocyclic ring systems is exploited in the first enantioselective total synthesis of bacilosarcins A and B, which has been achieved in simple two‐step sequences from amicoumacin C. Bacilosarcin A incorporates a totally unprecedented heterobicyclic ring system and exhibits a remarkably potent herbicidal activity.

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Synthetic studies on β-lactam antibiotics. VII. Mild removal of the benzyl ester protecting group with aluminum trichloride

Cited by 95 publications

References 7 publications

Synthesis of the β-Lactamase Indicators Cefesone and Nitrocefin

Synthesis of the β-Lactamase Indicators Cefesone and Nitrocefin

Deprotection of N‐tert‐Butoxycarbonyl (Boc) Protected Functionalized Heteroarenes via Addition–Elimination with 3‐Methoxypropylamine

Total Synthesis of Bacilosarcins A and B

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