Published: August 29, 2011 r2011 American Chemical Society 8082 dx.doi.org/10.1021/jo201395n | J. Org. Chem. 2011, 76, 8082–8087 NOTE pubs.acs.org/joc Synthesis of Balsaminone A, a Naturally Occurring Pentacyclic Dinaphthofuran Quinone Jalindar Padwal, William Lewis, and Christopher J. Moody* School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD, U.K. b S Supporting Information Q uinones, particularly naphthoquinones, are widespread in nature 1 and are essential for many life processes. Although quinones, a large group of natural pigments, do contribute to natural color, their major role is in redox processes. For example, pyrroloquinoline quinone (PQQ) is a redox cofactor, and the naphthoquinone phylloquinone (vitamin K 1 ) occurs in green plants and participates in photosynthetic electron transport. Other quinone natural products also possess potent biological activity: for example, adriamycin (doxorubicin) is a front-line cancer chemotherapy treatment. In 1998, two unusual dinaphthofuran quinone derivatives named balsaminone A (1a) and B (1b) were isolated from the pericarp of fruit of Impatiens balsamina L. (Balsaminaceae) (garden or rose balsam, sometimes known as touch-me-not) together with the known compound 2-methoxy-1,4-naphthoquinone. 2 The compounds have significant antipruritic activity, and the aerial parts of the plant have been used for the treatment of articular rheumatism, bruises, and beri-beri in Chinese traditional medicine. Balsaminone A was isolated as red needles that decomposed gradually in air but more rapidly in chloroform solution. The structure was determined to be 5-hydroxy-6- methoxydinaphtho[2,3-b:2 0 ,1 0 -d]furan-7,12-dione (1a) by a combination of spectroscopic methods. Balsaminone B was determined to be the corresponding β-D-glucoside 1b (Figure 1). Our own interest in quinone natural products dates back to an early synthesis of coenzyme PQQ 3 and more recently to other families of benzoquinones, 49 and we now report the first synthesis of balsaminone A. Over a century ago, Liebermann reported that the reaction of 2,3-dichloro-1,4-naphthoquinone (2) with resorcinol gave naphthofuran 3. 10 The reaction has subsequently been used by others in routes to substituted naphthoquinones 11 and a range of tetra- and pentacyclic napthoquinone compounds with antic- ancer activity, 1214 and therefore it seemed reasonable that balsaminone A (1a) could be formed from a suitable precursor 4 that itself resulted from reaction of naphthoquinone 2 with an appropriate 1,4-dihydroxynaphthalene 5, where the R group can be converted into a methoxy group following the formation of the pentacyclic system (Scheme 1). In considering the choice of 1,4-dihydroxynaphthalene start- ing material 5, ideally a methoxy group or other oxygen-contain- ing functionality was needed as the 2-substituent, R. A range of such compounds 5 (R = OMe, OH, OAc, OMs) was prepared, but all failed to condense with 2,3-dichloronaphthoquinone 2. Therefore, it was decided to investigate substituents, R, that possessed different electronic properties, starting with an acetyl group on the basis that a subsequent BaeyerVilliger reaction would deliver the required oxygen functionality. Thus, 2-acetyl-1,4-dihydroxynaphthalene (6), most conveni- ently prepared by boron tri fluoride mediated Fries rearrangement of 1,4-diacetoxynaphthalene, 15 was reacted with 2,3-dichloronaphtho- quinone (2) in pyridine in the presence of potassium carbonate. Pleas- ingly, this reaction proceeded smoothly and gave the desired penta- cyclic dinaphthofuran quinone 7 in good yield, the structure of which was confirmed by X-ray crystallography (Figure 2). Subsequent ben- zylation gave the corresponding benzyloxy compound 8 (Scheme 2). Figure 1. Balsaminones A (1a) and B (1b) isolated from the pericarp of fruit of the I. balsamina L. (Balsaminaceae). Received: July 6, 2011 ABSTRACT: A short synthesis of the natural product balsami- none A, a dinaphthofuran quinone, is described. The key steps of the synthesis are base-induced coupling of 1,4-dihydroxy-2- naphthaldehyde with 2,3-dichloronaphthoquinone to give a pentacyclic dinaphthofuran directly, followed by conversion of the aldehyde into the desired methoxy group via the corresponding phenol. The synthesis, in which the structure of a key pentacyclic intermediate is corroborated by X-ray crystallography, confirms the original structural assignment of the natural product.