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The "Spice Islands" and China

The Portuguese continued sailing eastward from India, entering a second existing circuit of the Indian Ocean trade, from Calicut and Quillon in India, to southeast Asia, including Malacca, and Palembang. In 1511, Afonso de Albuquerque conquered Malacca for Portugal, then the center of Asian trade. East of Malacca, Albuquerque sent several diplomatic missions: Duarte Fernandes as the first European envoy to the Kingdom of Siam (modern Thailand).

Learning the location of the so-called "spice islands", heretofore a secret from the Europeans, were the Maluku Islands, mainly the Banda, then the world's only source of nutmeg and cloves. Reaching these was the main purpose for the Portuguese voyages in the Indian Ocean. Albuquerque sent an expedition led by António de Abreu to Banda (via Java and the Lesser Sunda Islands), where they were the first Europeans to arrive in early 1512, after taking a route through which they also reached first the islands of Buru, Ambon and Seram. From Banda Abreu returned to Malacca, while his vice-captain Francisco Serrão, after a separation forced by a shipwreck and heading north, reached once again Ambon and sank off Ternate, where he obtained a license to build a Portuguese fortress-factory: the Fort of São João Baptista de Ternate, which founded the Portuguese presence in the Malay Archipelago.

In May 1513 Jorge Álvares, one of the Portuguese envoys, reached China. Although he was the first to land on Lintin Island in the Pearl River Delta, it was Rafael Perestrello —a cousin of the famed Christopher Columbus —who became the first European explorer to land on the southern coast of mainland China and trade in Guangzhou in 1516, commanding a Portuguese vessel with crew from a Malaccan junk that had sailed from Malacca. Fernão Pires de Andrade visited Canton in 1517 and opened up trade with China. The Portuguese were defeated by the Chinese in 1521 at the Battle of Tunmen and in 1522 at the Battle of Xicaowan, during which the Chinese captured Portuguese breech-loading swivel guns and reverse engineered the technology, calling them "Folangji" 佛郎機 (Frankish) guns, since the Portuguese were called "Folangji" by the Chinese. After a few decades, hostilities between the Portuguese and Chinese ceased and in 1557 the Chinese allowed the Portuguese to occupy Macau.

To enforce a trade monopoly, Muscat and Hormuz in the Persian Gulf were seized by Afonso de Albuquerque in 1507 and in 1515, respectively. He also entered into diplomatic relations with Persia. In 1513, while trying to conquer Aden, an expedition led by Albuquerque cruised the Red Sea inside the Bab al-Mandab, and sheltered at Kamaran island. In 1521, a force under António Correia conquered Bahrain, ushering in a period of almost eighty years of Portuguese rule of the Gulf archipelago. In the Red Sea, Massawa was the most northerly point frequented by the Portuguese until 1541, when a fleet under Estevão da Gama penetrated as far as Suez.