Download New aniline photocage for carboxylic acids

25th Croatian meeting of chemists and chemical engineers, Poreč, 2017.
New aniline photocage for carboxylic acids
Nova anilinska fotouklonjiva zaštitna skupina za karboksilne kiseline
Đani Škalamera, Vesna Blažek Bregović, Nikola Basarić
Department of Organic Chemistry and Biochemistry, Ruđer Bošković Institute,
Bijenička cesta 54, Zagreb, Croatia
E-mail: [email protected]
Photocleavable protecting groups (PPGs, photocages) are extensively used in chemical and
biological sciences. It was shown that they can be used for light-controlled small molecule
release (NO, H2S, CO, HNO) in biological systems [1], photocontrolled targeted drug delivery
[2] and in molecular imaging and cell biology [3].
Very important area for application of PPGs is organic synthesis. Typical protecting groups
used in organic synthesis (e.g. Boc, Fmoc) require some specific reagents/conditions for their
removal. On the other hand, for removal of PPGs only iradiation is required (usually UV),
which is big advantage in comparison with the standard protecting groups. Three main
classes of PPGs described in the literature are based on: 2-nitrobenzyl, carbonyl or benzyl
moieties.[4] However, these PPGs suffer from some limitations in their application, e. g. for
2-nitrobenzylalcohols the decaging reaction is slow. Therefore, research for new PPGs is very
important topic of current research in organic photochemistry.
Wang et al. have recently reported an interesting example of photocage for alcohols, based
on m-hydroxyaniline ethers.[5] We decided to further develop this type of protecting group
and expand their application for the protection of carboxylic acids. A systematic study of
photochemical reactivity was conducted on o-, m- and p-substituted aniline-based PPGs. We
have found out that a range of structurally different carboxylic acids can be easily converted
to o-hydroxymehtylaniline esters ih high yield. The photodeprotection was accomplished
under mild conditions (aqueous CH3CN), using 300 nm light. After the photodecageing, only
aqueous workup (extraction) was required to obtain pure acid, without the need for the
product chromatographic purification or crystallization. Furthermore, we have
demonstrated that aniline alcohol can be regenerated from the photodeprotection reaction
and reused.
NMe 2
h (300 nm)
O
R
O
NMe2
O
+
CH 3CN-H 2O (4:1)
R
OH
O
OH
easily removed by
extraction workup
R
OH
=
ibuprofen
Boc-Phe-OH
Cbz-GABA-OH
BnO(O)C(CH2)4COOH
1-Ad-COOH
Figure 1: Photodeprotection of carboxylic acid protected with new aniline photocage.
References
[1] H. Nakagawa, Chem. Pharm. Bull. 64 (2016) 1249–1255.
[2] N.-C. Fan, F.-Y. Cheng, J.A. Ho and C.-S. Yeh, Angew. Chem. Int. Ed. 51 (2012) 8806-8810.
[3] Q. Shao and B. Xing, Chem. Soc. Rev. 39 (2010) 2835–2846.
[4] P. Klan, T. Šolomek, C. G. Bochet, A. Blanc, R. Givens, M. Rubina, V. Popik, A. Kostikov, J. Wirz,
Chem.Rev. 113 (2013) 119-191.
[5] P. Wang, W. Lu, D.A. Devalankar and Z. Ding, Org. Lett. 17 (2015) 2114-2117.