Two new indole alkaloids, 20-epi-antirhine [4] and 19(S)-hydroxydihydrocorynantheol [6], have been isolated from Antirhea portoricensis (Rubiaceae), collected in the Caribbean. Structures have been established on the basis of spectral data. In addition, four known alkaloids have been isolated, namely, yohimbol [1], epi-yohimbol [2], antirhine [3] and iso-antirhine [5]. Antirhea portoricensis (Britton & Wilson) Standl. (Rubiaceae), formerly known as Stenostomum portoricense Britton & Wilson, is a small- or medium-sized endemic tree of Puerto Rico (1). As part of our continuing interest in Caribbean plants and the chemotaxonomy of West Indian Rubiaceae in particular (2), we report the isolation of two new indole alkaloids from this species.From the peeled roots (450 g), alkaloids were extracted by the usual process (see Experimental) furnishing 1.2 g of a crude alkaloid mixture (AM). Purification of alkaloids was performed by means of cc and prep. tlc. Six alkaloids were isolated. They were, in order of elution from Si gel, yohimbol [1] (3-5) (1.2% of AM), epi-yohimbol [2] (3-5) (1.2%), antirhine [3] (6,7) (2.5%), 20-epi-antirhine [4] (1.8%), iso-antirhine [5] (8) (2.3%) and 19(S)-hydroxydihydrocorynantheol [6] (0.8%). Compounds 1, 2, 3 and 5 were identified through their spectral and physical properties (ir, uv, nmr, mass spectra, [α]D). Alkaloids 4 and 6 are new. As the spectral data of compounds 1, 2 and 5 are incompletely described in the literature, the complete assignments of their ¹H- and ¹³C-nmr spectra are given in the Experimental section.Alkaloid 4 was isolated as an amorphous compound [α]²⁵D +57° (c 0.5, CHCl₃). The eims showed a molecular ion at m/z 296, which was analyzed by hrms for C₁₉H₂₄N₂O and exhibited the same fragmentation pattern as antirhine (6,7). Examination of the ¹H-nmr spectrum of 4 revealed the presence of a deshielded broad resonance at δ 4.04, which could be attributed to a proton (H-3) located at the ring junction of a cis-quinolizidine. The configuration of C-15 is assumed to be 15S as found in antirhine for biogenetic reasons. Coupling constant values of H-14 indicated that 4 and antirhine possess the same C-3 and C-15 configurations. The most significant differences with antirhine were observed for the H-21 and H-14 chemical shifts (see Experimental). Examination of the ¹³C-nmr spectrum of 4 showed great similarity with that of 3. Therefore, the structure 20-epi-antirhine was proposed for this novel alkaloid. Its formation presumably resulted from a C-20 epimerization of the biogenetic aldehyde precursor.The other new alkaloid [6] was isolated in minor amounts [α]²⁵D -3° (c 0.6, MeOH), displaying an [M]⁺ at m/z 314 (C₁₉H₂₆N₂O₂ from hrms) and a uv spectrum (λ max 214 and 281 nm) characteristic of an indole chromophore. Its ir spectrum indicated the presence of an NH and/or OH group (3300 cm⁻¹). The ¹H-nmr spectrum exhibited four aromatic protons and nineteen aliphatic protons identified by 2D nmr experiments. The ¹H- and ¹³C-nmr spectra showed α-OH ethyl side-chain signals (Me-18 δ 1.19, δ 16.91 and CH-19 δ 4.27, δ 66.92) and β-OH ethyl side-chain signals (CH₂-17 OH δ 3.80, δ 60.27 and CH₂-16 δ 1.47 and 2.00, δ 36.16). The complete assignments were performed using homo- and heteronuclear 2D nmr experiments and were consistent with a dihydrocorynantheol skeleton. From these data, compound 6 was concluded to be 19-hydroxydihydrocorynantheol. Although no data exist for 19-hydroxycorynantheol derivatives, the S configuration of C-19 was deduced through comparison of the chemical shifts and coupling constants of compounds of analogous substitution in other series (9,10). 11-Methoxy-19-hydroxydihydrocorynantheol has already been obtained by rearrangement of tetraphylline (11), but this is the first report of such a structure from a natural source.